Probenecid Inhibits the Human Bitter Taste Receptor TAS2R16 and Suppresses Bitter Perception of Salicin
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"Probenecid inhibits the human bitter taste receptor TAS2R16 and suppresses bitter perception of salicin", "type"=>"journal", "authors"=>[{"first_name"=>"Tiffani A.", "last_name"=>"Greene", "scopus_author_id"=>"7102116306"}, {"first_name"=>"Suzanne", "last_name"=>"Alarcon", "scopus_author_id"=>"35071102100"}, {"first_name"=>"Anu", "last_name"=>"Thomas", "scopus_author_id"=>"35216845900"}, {"first_name"=>"Eli", "last_name"=>"Berdougo", "scopus_author_id"=>"6507495536"}, {"first_name"=>"Benjamin J.", "last_name"=>"Doranz", "scopus_author_id"=>"6603437820"}, {"first_name"=>"Paul A S", "last_name"=>"Breslin", "scopus_author_id"=>"7003821177"}, {"first_name"=>"Joseph B.", "last_name"=>"Rucker", "scopus_author_id"=>"7005352092"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-79956347958", "pmid"=>"21629661", "sgr"=>"79956347958", "doi"=>"10.1371/journal.pone.0020123", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203", "pui"=>"361809183"}, "id"=>"1f9c01de-d32d-3eff-8a55-f16feb5f68d5", "abstract"=>"Bitter taste stimuli are detected by a diverse family of G protein-coupled receptors (GPCRs) expressed in gustatory cells. Each bitter taste receptor (TAS2R) responds to an array of compounds, many of which are toxic and can be found in nature. For example, human TAS2R16 (hTAS2R16) responds to β-glucosides such as salicin, and hTAS2R38 responds to thiourea-containing molecules such as glucosinolates and phenylthiocarbamide (PTC). While many substances are known to activate TAS2Rs, only one inhibitor that specifically blocks bitter receptor activation has been described. Here, we describe a new inhibitor of bitter taste receptors, p-(dipropylsulfamoyl)benzoic acid (probenecid), that acts on a subset of TAS2Rs and inhibits through a novel, allosteric mechanism of action. Probenecid is an FDA-approved inhibitor of the Multidrug Resistance Protein 1 (MRP1) transporter and is clinically used to treat gout in humans. Probenecid is also commonly used to enhance cellular signals in GPCR calcium mobilization assays. We show that probenecid specifically inhibits the cellular response mediated by the bitter taste receptor hTAS2R16 and provide molecular and pharmacological evidence for direct interaction with this GPCR using a non-competitive (allosteric) mechanism. Through a comprehensive analysis of hTAS2R16 point mutants, we define amino acid residues involved in the probenecid interaction that result in decreased sensitivity to probenecid while maintaining normal responses to salicin. Probenecid inhibits hTAS2R16, hTAS2R38, and hTAS2R43, but does not inhibit the bitter receptor hTAS2R31 or non-TAS2R GPCRs. Additionally, structurally unrelated MRP1 inhibitors, such as indomethacin, fail to inhibit hTAS2R16 function. Finally, we demonstrate that the inhibitory activity of probenecid in cellular experiments translates to inhibition of bitter taste perception of salicin in humans. This work identifies probenecid as a pharmacological tool for understanding the cell biology of bitter taste and as a lead for the development of broad specificity bitter blockers to improve nutrition and medical compliance.", "link"=>"http://www.mendeley.com/research/probenecid-inhibits-human-bitter-taste-receptor-tas2r16-suppresses-bitter-perception-salicin", "reader_count"=>67, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>3, "Researcher"=>17, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>1, "Student > Master"=>11, "Other"=>3, "Student > Bachelor"=>5, "Lecturer"=>4, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>3, "Researcher"=>17, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>1, "Student > Master"=>11, "Other"=>3, "Student > Bachelor"=>5, "Lecturer"=>4, "Professor"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>5, "Biochemistry, Genetics and Molecular Biology"=>6, "Agricultural and Biological Sciences"=>36, "Medicine and Dentistry"=>8, "Neuroscience"=>2, "Sports and Recreations"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>4, "Psychology"=>1, "Social Sciences"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Neuroscience"=>{"Neuroscience"=>2}, "Chemistry"=>{"Chemistry"=>4}, "Social Sciences"=>{"Social Sciences"=>1}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>36}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Unspecified"=>{"Unspecified"=>5}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Netherlands"=>3, "United States"=>1, "Denmark"=>1, "Spain"=>2}, "group_count"=>2}

CrossRef

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/79956347958"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/79956347958?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=79956347958&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=79956347958&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/79956347958", "dc:identifier"=>"SCOPUS_ID:79956347958", "eid"=>"2-s2.0-79956347958", "dc:title"=>"Probenecid inhibits the human bitter taste receptor TAS2R16 and suppresses bitter perception of salicin", "dc:creator"=>"Greene T.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"6", "prism:issueIdentifier"=>"5", "prism:pageRange"=>nil, "prism:coverDate"=>"2011-05-27", "prism:coverDisplayDate"=>"2011", "prism:doi"=>"10.1371/journal.pone.0020123", "citedby-count"=>"65", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"Integral Molecular, Inc.", "affiliation-city"=>"Philadelphia", "affiliation-country"=>"United States"}], "pubmed-id"=>"21629661", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e20123", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0020123", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Counter

  • {"month"=>"5", "year"=>"2011", "pdf_views"=>"22", "xml_views"=>"5", "html_views"=>"186"}
  • {"month"=>"6", "year"=>"2011", "pdf_views"=>"114", "xml_views"=>"1", "html_views"=>"348"}
  • {"month"=>"7", "year"=>"2011", "pdf_views"=>"30", "xml_views"=>"0", "html_views"=>"89"}
  • {"month"=>"8", "year"=>"2011", "pdf_views"=>"33", "xml_views"=>"0", "html_views"=>"97"}
  • {"month"=>"9", "year"=>"2011", "pdf_views"=>"32", "xml_views"=>"0", "html_views"=>"89"}
  • {"month"=>"10", "year"=>"2011", "pdf_views"=>"29", "xml_views"=>"0", "html_views"=>"84"}
  • {"month"=>"11", "year"=>"2011", "pdf_views"=>"29", "xml_views"=>"4", "html_views"=>"87"}
  • {"month"=>"12", "year"=>"2011", "pdf_views"=>"26", "xml_views"=>"0", "html_views"=>"75"}
  • {"month"=>"1", "year"=>"2012", "pdf_views"=>"28", "xml_views"=>"0", "html_views"=>"93"}
  • {"month"=>"2", "year"=>"2012", "pdf_views"=>"25", "xml_views"=>"0", "html_views"=>"71"}
  • {"month"=>"3", "year"=>"2012", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"115"}
  • {"month"=>"4", "year"=>"2012", "pdf_views"=>"23", "xml_views"=>"1", "html_views"=>"103"}
  • {"month"=>"5", "year"=>"2012", "pdf_views"=>"33", "xml_views"=>"0", "html_views"=>"106"}
  • {"month"=>"6", "year"=>"2012", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"85"}
  • {"month"=>"7", "year"=>"2012", "pdf_views"=>"22", "xml_views"=>"0", "html_views"=>"89"}
  • {"month"=>"8", "year"=>"2012", "pdf_views"=>"18", "xml_views"=>"4", "html_views"=>"73"}
  • {"month"=>"9", "year"=>"2012", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"94"}
  • {"month"=>"10", "year"=>"2012", "pdf_views"=>"25", "xml_views"=>"1", "html_views"=>"85"}
  • {"month"=>"11", "year"=>"2012", "pdf_views"=>"18", "xml_views"=>"1", "html_views"=>"112"}
  • {"month"=>"12", "year"=>"2012", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"79"}
  • {"month"=>"1", "year"=>"2013", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"107"}
  • {"month"=>"2", "year"=>"2013", "pdf_views"=>"16", "xml_views"=>"2", "html_views"=>"125"}
  • {"month"=>"3", "year"=>"2013", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"89"}
  • {"month"=>"4", "year"=>"2013", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"124"}
  • {"month"=>"5", "year"=>"2013", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"76"}
  • {"month"=>"6", "year"=>"2013", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"78"}
  • {"month"=>"7", "year"=>"2013", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"60"}
  • {"month"=>"8", "year"=>"2013", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"49"}
  • {"month"=>"9", "year"=>"2013", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"75"}
  • {"month"=>"10", "year"=>"2013", "pdf_views"=>"13", "xml_views"=>"1", "html_views"=>"314"}
  • {"month"=>"11", "year"=>"2013", "pdf_views"=>"46", "xml_views"=>"0", "html_views"=>"269"}
  • {"month"=>"12", "year"=>"2013", "pdf_views"=>"23", "xml_views"=>"0", "html_views"=>"122"}
  • {"month"=>"1", "year"=>"2014", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"66"}
  • {"month"=>"2", "year"=>"2014", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"91"}
  • {"month"=>"3", "year"=>"2014", "pdf_views"=>"13", "xml_views"=>"2", "html_views"=>"153"}
  • {"month"=>"4", "year"=>"2014", "pdf_views"=>"17", "xml_views"=>"1", "html_views"=>"166"}
  • {"month"=>"5", "year"=>"2014", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"127"}
  • {"month"=>"6", "year"=>"2014", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"132"}
  • {"month"=>"7", "year"=>"2014", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"93"}
  • {"month"=>"8", "year"=>"2014", "pdf_views"=>"8", "xml_views"=>"2", "html_views"=>"57"}
  • {"month"=>"9", "year"=>"2014", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"101"}
  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"73"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"71"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"10", "xml_views"=>"2", "html_views"=>"61"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"127"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"36"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"48"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"68"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"61"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"70"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"48"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"49"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"112"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"95"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"99"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"102"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"138"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"80"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"85"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"102"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"65"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"37"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"91"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"56"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"62"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"90", "xml_views"=>"0", "html_views"=>"86"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"56"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"38"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"59"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"72"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"11", "xml_views"=>"2", "html_views"=>"82"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"67"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"37"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"58"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"52"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"2", "html_views"=>"49"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"2", "html_views"=>"53"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"3", "html_views"=>"69"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"55"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"7", "xml_views"=>"2", "html_views"=>"37"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"13", "xml_views"=>"1", "html_views"=>"51"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"2", "html_views"=>"21"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"20", "xml_views"=>"2", "html_views"=>"41"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"20", "xml_views"=>"3", "html_views"=>"40"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"24"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"35"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"2", "html_views"=>"16"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"25"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"2", "xml_views"=>"2", "html_views"=>"17"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"12"}
  • {"month"=>"9", "year"=>"2019", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"22"}
  • {"month"=>"10", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"16"}
  • {"month"=>"11", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"12", "year"=>"2019", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"2"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/772670"], "description"=>"<p>HEK-293T cells were transiently transfected with Gα16gust44 and the indicated TAS2R receptor. 22 hours post-transfection, calcium influx was measured after challenge with (A) 3 mM salicin or (B) 100 µM PTC in the presence or absence of the indicated compounds (1 mM, pretreatment for 60 minutes). Error bars represent standard deviations (n = 6 for hTAS2R16; n = 12 for hTAS2R38).</p>", "links"=>[], "tags"=>["probenecid", "analogs", "activation", "htas2r16", "htas2r38"], "article_id"=>443034, "categories"=>["Biological Sciences", "Biochemistry", "Mental Health", "Biotechnology", "Pharmacology", "Physiology", "Molecular Biology", "Neuroscience"], "users"=>["Tiffani A. Greene", "Suzanne Alarcon", "Anu Thomas", "Eli Berdougo", "Benjamin J. Doranz", "Paul A. S. Breslin", "Joseph B. Rucker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020123.g006", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differential_effect_of_probenecid_analogs_on_the_activation_of_hTAS2R16_and_hTAS2R38_receptors_/443034", "title"=>"Differential effect of probenecid analogs on the activation of hTAS2R16 and hTAS2R38 receptors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-24 00:50:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/387559"], "description"=>"<div><p>Bitter taste stimuli are detected by a diverse family of G protein-coupled receptors (GPCRs) expressed in gustatory cells. Each bitter taste receptor (TAS2R) responds to an array of compounds, many of which are toxic and can be found in nature. For example, human TAS2R16 (hTAS2R16) responds to β-glucosides such as salicin, and hTAS2R38 responds to thiourea-containing molecules such as glucosinolates and phenylthiocarbamide (PTC). While many substances are known to activate TAS2Rs, only one inhibitor that specifically blocks bitter receptor activation has been described. Here, we describe a new inhibitor of bitter taste receptors, <em>p</em>-(dipropylsulfamoyl)benzoic acid (probenecid), that acts on a subset of TAS2Rs and inhibits through a novel, allosteric mechanism of action. Probenecid is an FDA-approved inhibitor of the Multidrug Resistance Protein 1 (MRP1) transporter and is clinically used to treat gout in humans. Probenecid is also commonly used to enhance cellular signals in GPCR calcium mobilization assays. We show that probenecid specifically inhibits the cellular response mediated by the bitter taste receptor hTAS2R16 and provide molecular and pharmacological evidence for direct interaction with this GPCR using a non-competitive (allosteric) mechanism. Through a comprehensive analysis of hTAS2R16 point mutants, we define amino acid residues involved in the probenecid interaction that result in decreased sensitivity to probenecid while maintaining normal responses to salicin. Probenecid inhibits hTAS2R16, hTAS2R38, and hTAS2R43, but does not inhibit the bitter receptor hTAS2R31 or non-TAS2R GPCRs. Additionally, structurally unrelated MRP1 inhibitors, such as indomethacin, fail to inhibit hTAS2R16 function. Finally, we demonstrate that the inhibitory activity of probenecid in cellular experiments translates to inhibition of bitter taste perception of salicin in humans. This work identifies probenecid as a pharmacological tool for understanding the cell biology of bitter taste and as a lead for the development of broad specificity bitter blockers to improve nutrition and medical compliance.</p> </div>", "links"=>[], "tags"=>["probenecid", "inhibits", "receptor", "tas2r16", "suppresses", "salicin"], "article_id"=>136538, "categories"=>["Biological Sciences", "Biochemistry", "Mental Health", "Biotechnology", "Pharmacology", "Physiology", "Molecular Biology", "Neuroscience"], "users"=>["Tiffani A. Greene", "Suzanne Alarcon", "Anu Thomas", "Eli Berdougo", "Benjamin J. Doranz", "Paul A. S. Breslin", "Joseph B. Rucker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020123", "stats"=>{"downloads"=>5, "page_views"=>96, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Probenecid_Inhibits_the_Human_Bitter_Taste_Receptor_TAS2R16_and_Suppresses_Bitter_Perception_of_Salicin/136538", "title"=>"Probenecid Inhibits the Human Bitter Taste Receptor TAS2R16 and Suppresses Bitter Perception of Salicin", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-24 01:48:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/772138"], "description"=>"<p>HEK-293T cells were transiently transfected with Gα16gust44 and the indicated TAS2R receptors in a 384-well microplate. 22 hours post-transfection, calcium influx was measured in cells challenged with the indicated ligands in the presence (closed triangles) or absence (open diamonds) of probenecid (1 mM; 1 hour pre-incubation). Probenecid treatment completely attenuated (A) salicin-dependent (3 mM) calcium influx by the hTAS2R16 receptor and (B) PTC- (100 µM) and (C) PROP-dependent (30 µM) calcium influx by the hTAS2R38 receptor. (D) Probenecid treatment similarly attenuated aloin-induced (3 mM) hTAS2R43 signaling. (E) Probenecid treatment did not inhibit saccharin induced signaling of hTAS2R31. (F) hTAS2R38 transfected cells challenged with probenecid or buffer alone (1 mM) did not result in calcium influx, but do flux with the PTC control.</p>", "links"=>[], "tags"=>["htas2r43"], "article_id"=>442502, "categories"=>["Biological Sciences", "Biochemistry", "Mental Health", "Biotechnology", "Pharmacology", "Physiology", "Molecular Biology", "Neuroscience"], "users"=>["Tiffani A. Greene", "Suzanne Alarcon", "Anu Thomas", "Eli Berdougo", "Benjamin J. Doranz", "Paul A. S. Breslin", "Joseph B. Rucker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020123.g001", "stats"=>{"downloads"=>2, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inhibition_of_hTAS2R16_hTAS2R38_and_hTAS2R43_by_probenecid_/442502", "title"=>"Inhibition of hTAS2R16, hTAS2R38, and hTAS2R43 by probenecid.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-24 00:41:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/772733"], "description"=>"<p>(A) HEK-293T cells were transiently transfected with wild type hTAS2R16 and Gα16gust44. 22 hours post-transfection, calcium flux was measured for cells that were challenged with 3 mM salicin in the presence (closed triangles) or absence (open diamonds) of probenecid (1 mM; 1 hour pre-incubation). Salicin response to mock transfected (vector alone) HEK-293T cells is shown for comparison. (B, C) HEK-293T cells were similarly transfected with hTAS2R16 variants containing the mutations N96T or P44T/H113R, and challenged with 3 mM salicin in the presence or absence of probenecid (1 mM; 1 hour pre-incubation). N96T and P44T/H113R mutants showed decreased sensitivity to probenecid. A separate clone containing the single point mutant H113R was also tested to rule out this residue (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0020123#pone.0020123.s001\" target=\"_blank\">Figure S1</a>). Error bars represent standard deviations (n = 4).</p>", "links"=>[], "tags"=>["htas2r16", "residues", "probenecid"], "article_id"=>443096, "categories"=>["Biological Sciences", "Biochemistry", "Mental Health", "Biotechnology", "Pharmacology", "Physiology", "Molecular Biology", "Neuroscience"], "users"=>["Tiffani A. Greene", "Suzanne Alarcon", "Anu Thomas", "Eli Berdougo", "Benjamin J. Doranz", "Paul A. S. Breslin", "Joseph B. Rucker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020123.g007", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identification_of_hTAS2R16_residues_required_for_probenecid_inhibition_/443096", "title"=>"Identification of hTAS2R16 residues required for probenecid inhibition.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-24 00:51:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/772382"], "description"=>"<p>HEK-293T cells were transiently transfected with Gα16gust44 and the indicated GPCR receptors. In the case of the endogenously expressed βAR receptor, only Gα16gust44 was transfected. 22 hours post-transfection, calcium influx was measured for cells that were challenged with the indicated ligands in the presence (closed triangles) or absence (open diamonds) of probenecid (1 mM; 1 hour pre-incubation). Probenecid treatment did not attenuate calcium influx upon challenge of (A) CCR5 with 10 nM RANTES, (B) CXCR4 with 10 nM SDF-1α, or (C) βAR with 10 µM isoproterenol.</p>", "links"=>[], "tags"=>["gpcrs", "inhibited"], "article_id"=>442748, "categories"=>["Biological Sciences", "Biochemistry", "Mental Health", "Biotechnology", "Pharmacology", "Physiology", "Molecular Biology", "Neuroscience"], "users"=>["Tiffani A. Greene", "Suzanne Alarcon", "Anu Thomas", "Eli Berdougo", "Benjamin J. Doranz", "Paul A. S. Breslin", "Joseph B. Rucker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020123.g003", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Non_Gustatory_GPCRs_are_not_inhibited_by_probenecid_/442748", "title"=>"Non-Gustatory GPCRs are not inhibited by probenecid.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-24 00:45:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/772602"], "description"=>"<p>(A) HEK-293T cells were transiently transfected with Gα16gust44 and hTAS2R16 or hTAS2R38. 22 hours post-transfection, cells were pre-treated with increasing amounts of probenecid for 1 hour followed by challenge with 3 mM salicin or 300 µM PTC. (B) HEK-293T cells were transiently transfected with Gα16gust44 and hTAS2R16, pre-treated with increasing amounts of probenecid for 1 hour, and then challenged with different concentrations of salicin. Error bars represent standard errors (n = 4). (C) HEK-293T cells were transiently transfected with Gα16gust44 and hTAS2R38, pre-treated with increasing amounts of probenecid for 1 hour, and then challenged with different concentrations of PTC. Error bars represent standard errors (n = 4).</p>", "links"=>[], "tags"=>["probenecid"], "article_id"=>442967, "categories"=>["Biological Sciences", "Biochemistry", "Mental Health", "Biotechnology", "Pharmacology", "Physiology", "Molecular Biology", "Neuroscience"], "users"=>["Tiffani A. Greene", "Suzanne Alarcon", "Anu Thomas", "Eli Berdougo", "Benjamin J. Doranz", "Paul A. S. Breslin", "Joseph B. Rucker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020123.g005", "stats"=>{"downloads"=>2, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pharmacological_mechanism_of_action_of_probenecid_inhibition_/442967", "title"=>"Pharmacological mechanism of action of probenecid inhibition.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-24 00:49:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/772287"], "description"=>"<p>Structures of TAS2R agonists, probenecid, MRP1 inhibitors, and probenecid analogs used.</p>", "links"=>[], "tags"=>["tas2r", "mrp1", "probenecid", "analogs"], "article_id"=>442648, "categories"=>["Biological Sciences", "Biochemistry", "Mental Health", "Biotechnology", "Pharmacology", "Physiology", "Molecular Biology", "Neuroscience"], "users"=>["Tiffani A. Greene", "Suzanne Alarcon", "Anu Thomas", "Eli Berdougo", "Benjamin J. Doranz", "Paul A. S. Breslin", "Joseph B. Rucker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020123.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Structures_of_TAS2R_agonists_probenecid_MRP1_inhibitors_and_probenecid_analogs_used_/442648", "title"=>"Structures of TAS2R agonists, probenecid, MRP1 inhibitors, and probenecid analogs used.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-24 00:44:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/772450"], "description"=>"<p>(A) HEK-293T cells were transiently transfected with hTAS2R16 and Gα16gust44. 22 hours post-transfection, calcium influx was measured for cells that were challenged with 3 mM salicin in the presence of 1 mM probenecid pretreatment for the indicated amount of time (0 min indicates co-injection of salicin with probenecid). hTAS2R16 was completely inactivated by 5 minutes of probenecid pretreatment. (B) HEK-293T cells were transiently transfected with hTAS2R16 and Gα16gust44 followed by challenge with 3 mM salicin in the presence or absence of the indicated compounds (1 mM, pretreatment for 60 minutes). The MRP1 transporter inhibitor indomethacin did not inhibit hTAS2R16 function. Error bars represent standard errors (n = 3).</p>", "links"=>[], "tags"=>["inhibition", "htas2r16", "occurs", "mrp1"], "article_id"=>442806, "categories"=>["Biological Sciences", "Biochemistry", "Mental Health", "Biotechnology", "Pharmacology", "Physiology", "Molecular Biology", "Neuroscience"], "users"=>["Tiffani A. Greene", "Suzanne Alarcon", "Anu Thomas", "Eli Berdougo", "Benjamin J. Doranz", "Paul A. S. Breslin", "Joseph B. Rucker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020123.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Probenecid_inhibition_of_hTAS2R16_occurs_rapidly_and_is_not_dependent_on_the_MRP1_transporter_/442806", "title"=>"Probenecid inhibition of hTAS2R16 occurs rapidly and is not dependent on the MRP1 transporter.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-24 00:46:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/772788"], "description"=>"<p>(A) 15 human subjects were asked to rate the bitterness intensity of 10 mM salicin before (pre) and after (post) treatment with 10 mM probenecid or control treatment with 8.1 µM quinine HCl (QHCl) on a general labeled magnitude scale (gLMS). Treatment with probenecid (black bars) significantly inhibited the perceived bitterness of salicin (p<0.05), whereas a bitter taste control treatment with QHCl had no affect (white bars). (B) 9 human subjects were asked to rate the bitterness intensity of 10 mM salicin or 250 mM saccharin before (pre) and after (post) treatment with 10 mM probenecid or control treatment with 8.1 µM quinine HCl (QHCl). Treatment with probenecid (black bars) significantly inhibited the perceived bitterness of salicin (p<0.05), whereas a control treatment with QHCl had no affect (white bars). Probenecid failed to inhibit the bitterness of saccharin (in the presence of the sweet taste inhibitor lactisole (lac) to enable subjects to focus exclusively on the bitterness of saccharin). The inhibitory effect of probenecid on salicin was also observed in the presence of lactisole, demonstrating that lactisole did not interfere with probenecid's inhibition of perceived bitterness. At the concentrations used, salicin and saccharin did not differ in their overall perceived bitterness. Error bars represent standard errors (SE).</p>", "links"=>[], "tags"=>["bitterness", "salicin"], "article_id"=>443154, "categories"=>["Biological Sciences", "Biochemistry", "Mental Health", "Biotechnology", "Pharmacology", "Physiology", "Molecular Biology", "Neuroscience"], "users"=>["Tiffani A. Greene", "Suzanne Alarcon", "Anu Thomas", "Eli Berdougo", "Benjamin J. Doranz", "Paul A. S. Breslin", "Joseph B. Rucker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020123.g008", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Suppression_of_human_bitterness_perception_of_salicin_by_probenecid_/443154", "title"=>"Suppression of human bitterness perception of salicin by probenecid.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-24 00:52:34"}

PMC Usage Stats | Further Information

  • {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"3", "full-text"=>"57", "year"=>"2011", "pdf"=>"38", "unique-ip"=>"52", "figure"=>"12", "scanned-summary"=>"0", "supp-data"=>"2"}
  • {"scanned-page-browse"=>"0", "month"=>"7", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"38", "unique-ip"=>"42", "pdf"=>"24", "year"=>"2011", "figure"=>"20", "scanned-summary"=>"0", "supp-data"=>"2"}
  • {"month"=>"8", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"52", "year"=>"2011", "pdf"=>"19", "unique-ip"=>"43", "figure"=>"13", "scanned-summary"=>"0", "supp-data"=>"1"}
  • {"scanned-page-browse"=>"0", "month"=>"9", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"36", "unique-ip"=>"26", "pdf"=>"18", "year"=>"2011", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"10", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"44", "year"=>"2011", "pdf"=>"27", "unique-ip"=>"39", "figure"=>"11", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"11", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"54", "unique-ip"=>"42", "pdf"=>"29", "year"=>"2011", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"12", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"20", "year"=>"2011", "pdf"=>"16", "unique-ip"=>"20", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"1", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"36", "unique-ip"=>"22", "pdf"=>"20", "year"=>"2012", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"2", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"45", "year"=>"2012", "pdf"=>"15", "unique-ip"=>"29", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"3", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"37", "unique-ip"=>"37", "pdf"=>"19", "year"=>"2012", "figure"=>"6", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"4", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"30", "year"=>"2012", "pdf"=>"14", "unique-ip"=>"24", "figure"=>"1", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"5", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"25", "unique-ip"=>"26", "pdf"=>"19", "year"=>"2012", "figure"=>"11", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"17", "year"=>"2012", "pdf"=>"24", "unique-ip"=>"20", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"unique-ip"=>"28", "full-text"=>"30", "pdf"=>"9", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2012", "month"=>"7"}
  • {"unique-ip"=>"27", "full-text"=>"30", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"8"}
  • {"unique-ip"=>"20", "full-text"=>"19", "pdf"=>"7", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"9"}
  • {"unique-ip"=>"21", "full-text"=>"23", "pdf"=>"11", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"10"}
  • {"unique-ip"=>"12", "full-text"=>"13", "pdf"=>"6", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"12"}
  • {"unique-ip"=>"17", "full-text"=>"19", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"1"}
  • {"unique-ip"=>"19", "full-text"=>"18", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"3"}
  • {"unique-ip"=>"23", "full-text"=>"24", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"2"}
  • {"unique-ip"=>"23", "full-text"=>"25", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2013", "month"=>"4"}
  • {"unique-ip"=>"40", "full-text"=>"38", "pdf"=>"12", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2012", "month"=>"11"}
  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
  • {"unique-ip"=>"14", "full-text"=>"16", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
  • {"unique-ip"=>"15", "full-text"=>"13", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
  • {"unique-ip"=>"10", "full-text"=>"17", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"2", "year"=>"2013", "month"=>"8"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
  • {"unique-ip"=>"27", "full-text"=>"39", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"16", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
  • {"unique-ip"=>"16", "full-text"=>"15", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
  • {"unique-ip"=>"15", "full-text"=>"16", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
  • {"unique-ip"=>"12", "full-text"=>"17", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"1"}
  • {"unique-ip"=>"7", "full-text"=>"9", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
  • {"unique-ip"=>"17", "full-text"=>"18", "pdf"=>"5", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
  • {"unique-ip"=>"21", "full-text"=>"20", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
  • {"unique-ip"=>"33", "full-text"=>"44", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"23", "full-text"=>"22", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
  • {"unique-ip"=>"20", "full-text"=>"20", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"25", "full-text"=>"32", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"17", "full-text"=>"23", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"23", "full-text"=>"20", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"15", "full-text"=>"14", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"24", "full-text"=>"32", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"17", "full-text"=>"17", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"19", "full-text"=>"15", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"21", "full-text"=>"19", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"24", "full-text"=>"20", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"23", "full-text"=>"17", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"22", "full-text"=>"19", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"15", "full-text"=>"11", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"12", "full-text"=>"15", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"21", "full-text"=>"22", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"16", "full-text"=>"14", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"22", "full-text"=>"18", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"11", "full-text"=>"20", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"15", "full-text"=>"19", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"25", "full-text"=>"28", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"25", "full-text"=>"23", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"17", "full-text"=>"15", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"19", "full-text"=>"21", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"15", "full-text"=>"13", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"17", "full-text"=>"17", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"12", "full-text"=>"14", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"17", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"15", "full-text"=>"17", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"30", "full-text"=>"32", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"18", "full-text"=>"19", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"17", "full-text"=>"20", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"16", "full-text"=>"14", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"24", "full-text"=>"27", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"16", "full-text"=>"24", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"17", "full-text"=>"16", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"34", "full-text"=>"37", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"15", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"17", "full-text"=>"19", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"23", "full-text"=>"23", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"17", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"19", "full-text"=>"30", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"2"}
  • {"unique-ip"=>"19", "full-text"=>"21", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"20", "full-text"=>"22", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"1", "cited-by"=>"1", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"15", "full-text"=>"17", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"41", "full-text"=>"35", "pdf"=>"9", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"13", "full-text"=>"19", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"32", "full-text"=>"32", "pdf"=>"8", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"16", "full-text"=>"19", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"17", "full-text"=>"19", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"20", "full-text"=>"25", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"25", "full-text"=>"25", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"21", "full-text"=>"20", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"14", "full-text"=>"16", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"18", "full-text"=>"20", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"24", "full-text"=>"26", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"16", "full-text"=>"15", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"16", "full-text"=>"21", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"20", "full-text"=>"24", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"2", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"16", "full-text"=>"18", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2019", "month"=>"10"}

Relative Metric

{"start_date"=>"2011-01-01T00:00:00Z", "end_date"=>"2011-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[304, 568, 702, 818, 927, 1027, 1118, 1206, 1285, 1357, 1427, 1500, 1564, 1636, 1705, 1773, 1840, 1909, 1974, 2039, 2106, 2170, 2234, 2296, 2358, 2423, 2484, 2546, 2606, 2673, 2734, 2795, 2857, 2921, 2984, 3046, 3100]}, {"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[290, 559, 698, 813, 927, 1028, 1121, 1206, 1289, 1360, 1433, 1501, 1569, 1637, 1707, 1774, 1841, 1911, 1974, 2038, 2103, 2161, 2219, 2280, 2345, 2406, 2466, 2529, 2592, 2654, 2713, 2772, 2835, 2893, 2954, 3020, 3071]}, {"subject_area"=>"/Biology and life sciences/Neuroscience", "average_usage"=>[306, 540, 664, 768, 864, 959, 1036, 1121, 1199, 1277, 1341, 1411, 1477, 1543, 1609, 1675, 1739, 1802, 1868, 1933, 1995, 2050, 2107, 2164, 2220, 2277, 2327, 2374, 2436, 2488, 2542, 2594, 2650, 2705, 2769, 2817, 2859]}, {"subject_area"=>"/Social sciences/Sociology", "average_usage"=>[426, 807, 983, 1078, 1202, 1297, 1394, 1505, 1611, 1713, 1819, 1918, 2007, 2092, 2190, 2261, 2341, 2445, 2522, 2612, 2692, 2754, 2830, 2908, 2987, 3076, 3157, 3246, 3319, 3431, 3527, 3602, 3670, 3725, 3772, 3821, 3879]}]}
Loading … Spinner
There are currently no alerts