Opioid-Induced Mitogen-Activated Protein Kinase Signaling in Rat Enteric Neurons following Chronic Morphine Treatment
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"Opioid-induced mitogen-activated protein kinase signaling in rat enteric neurons following chronic morphine treatment", "type"=>"journal", "authors"=>[{"first_name"=>"Celine", "last_name"=>"Duraffourd", "scopus_author_id"=>"25925648000"}, {"first_name"=>"Erica", "last_name"=>"Kumala", "scopus_author_id"=>"56380571900"}, {"first_name"=>"Laura", "last_name"=>"Anselmi", "scopus_author_id"=>"56210221500"}, {"first_name"=>"Nicholas C.", "last_name"=>"Brecha", "scopus_author_id"=>"7006102728"}, {"first_name"=>"Catia", "last_name"=>"Sternini", "scopus_author_id"=>"7005212716"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84907855745", "pui"=>"600125453", "sgr"=>"84907855745", "issn"=>"19326203", "pmid"=>"25302800", "doi"=>"10.1371/journal.pone.0110230"}, "id"=>"eba43f4d-f13b-3a2f-9f5c-1c54296e409e", "abstract"=>"Opioids, acting at μ opioid receptors, are commonly used for pain management. Chronic opioid treatment induces cellular adaptations, which trigger long-term side effects, including constipation mediated by enteric neurons. We tested the hypothesis that chronic opioid treatment induces alterations of μ opioid receptor signaling in enteric neurons, which are likely to serve as mechanisms underlying opioid-induced constipation. In cultured rat enteric neurons, either untreated (naïve) or exposed to morphine for 4 days (chronic), we compared the effect of morphine and DAMGO (D-Ala2,MePhe4,Gly-ol5 enkephalin) on μ opioid receptor internalization and downstream signaling by examining the activation of the mitogen-activated protein kinase/extracellular signal-regulated kinases 1 and 2 (MAPK/ERK) pathway, cAMP accumulation and transcription factor cAMP Response Element-Binding protein (CREB) expression. μ opioid receptor internalization and MAPK/ERK phosphorylation were induced by DAMGO, but not morphine in naïve neurons, and by both opioids in chronic neurons. MAPK/ERK activation was prevented by the receptor antagonist naloxone, by blocking receptor trafficking with hypertonic sucrose, dynamin inhibitor, or neuronal transfection with mutated dynamin, and by MAPK inhibitor. Morphine and DAMGO inhibited cAMP in naïve and chronic enteric neurons, and induced desensitization of cAMP signaling. Chronic morphine treatment suppressed desensitization of cAMP and MAPK signaling, increased CREB phosphorylation through a MAPK/ERK pathway and induced delays of gastrointestinal transit, which was prevented by MAPK/ERK blockade. This study showed that opioids induce endocytosis- and dynamin-dependent MAPK/ERK activation in enteric neurons and that chronic morphine treatment triggers changes at the receptor level and downstream signaling resulting in MAPK/ERK-dependent CREB activation. Blockade of this signaling pathway prevents the development of gastrointestinal motility impairment induced by chronic morphine treatment. These findings suggest that alterations in μ opioid receptor downstream signaling including MAPK/ERK pathway in enteric neurons chronically treated with morphine contribute to the development of opioid-induced constipation.", "link"=>"http://www.mendeley.com/research/opioidinduced-mitogenactivated-protein-kinase-signaling-rat-enteric-neurons-following-chronic-morphi-1", "reader_count"=>17, "reader_count_by_academic_status"=>{"Librarian"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>3, "Student > Master"=>4, "Student > Bachelor"=>3}, "reader_count_by_user_role"=>{"Librarian"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>3, "Student > Master"=>4, "Student > Bachelor"=>3}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>2, "Medicine and Dentistry"=>5, "Neuroscience"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Physics and Astronomy"=>1, "Psychology"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Neuroscience"=>{"Neuroscience"=>2}, "Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"Spain"=>1}, "group_count"=>1}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84907855745"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84907855745?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84907855745&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84907855745&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84907855745", "dc:identifier"=>"SCOPUS_ID:84907855745", "eid"=>"2-s2.0-84907855745", "dc:title"=>"Opioid-induced mitogen-activated protein kinase signaling in rat enteric neurons following chronic morphine treatment", "dc:creator"=>"Duraffourd C.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"9", "prism:issueIdentifier"=>"10", "prism:pageRange"=>nil, "prism:coverDate"=>"2014-10-10", "prism:coverDisplayDate"=>"10 October 2014", "prism:doi"=>"10.1371/journal.pone.0110230", "citedby-count"=>"17", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"David Geffen School of Medicine at UCLA", "affiliation-city"=>"Los Angeles", "affiliation-country"=>"United States"}], "pubmed-id"=>"25302800", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e110230", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0110230", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Twitter

Counter

  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"65", "xml_views"=>"9", "html_views"=>"204"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"18", "xml_views"=>"6", "html_views"=>"121"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"73"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"2", "html_views"=>"29"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"31"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"50"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"35"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"12"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"30"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"38"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"40"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"20", "xml_views"=>"1", "html_views"=>"25"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"21"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"2", "html_views"=>"23"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"72"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"68"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"2", "html_views"=>"22"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"29"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"12"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"3", "html_views"=>"17"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"1", "xml_views"=>"1", "html_views"=>"12"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"13"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"9", "year"=>"2019", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"5"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1713868"], "description"=>"<p>Naïve (A) and chronic (B) neurons were stimulated with 1 µM DAMGO, 10 µM morphine or medium (control) for 0–20 minutes. DAMGO and morphine induced a significant, transient CREB activation in chronic, but not naïve enteric neurons. CREB phosphorylation in chronic neurons was blocked by the MEK1/2 inhibitor (U0126) treatment. *p<0.05 and **p<0.01 vs. control; n = 4–7 experiments in triplicate per group. Representative gels of pCREB and CREB are shown at the bottom of the figure. Total CREB was used to verify that the treatment did not affect the total level of this protein and to confirm equal gel loading.</p>", "links"=>[], "tags"=>["morphine treatment triggers changes", "activation", "Chronic Morphine Treatment Opioids", "Rat Enteric Neurons", "creb", "Chronic opioid treatment", "receptor antagonist naloxone", "enteric neurons", "damgo", "pathway", "mapk", "Chronic morphine treatment"], "article_id"=>1201161, "categories"=>["Biological Sciences"], "users"=>["Céline Duraffourd", "Erica Kumala", "Laura Anselmi", "Nicholas C. Brecha", "Catia Sternini"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0110230.g006", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_opioids_on_CREB_phosphorylation_in_enteric_neurons_/1201161", "title"=>"Effect of opioids on CREB phosphorylation in enteric neurons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-10 03:49:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1713866"], "description"=>"<p>DAMGO-induced MAPK in naïve neurons is inhibited by dynasore, a dynamin inhibitor (A) and it is not observed in neurons transfected with mutated K44E dynamin (B). Both DAMGO- and morphine-induced MAPK activation in chronic neurons is blocked by dynasore (D) and is not detected in neurons transfected with mutated dynamin (E). C shows the increased expression of dynamin (dyn) immunoreactivity in enteric neurons transfected with wild type (WT) or mutated dynamin, confirming effectiveness of neuronal transfection. **p<0.01 compared to controls; n = 5–7 performed in triplicate per group. Representative immunoblots of dynamin immunoreactivities are shown at the bottom of histogram in C. GAPDH served as housekeeping protein to verify that the same amount of proteins was loaded on each gel.</p>", "links"=>[], "tags"=>["morphine treatment triggers changes", "activation", "Chronic Morphine Treatment Opioids", "Rat Enteric Neurons", "creb", "Chronic opioid treatment", "receptor antagonist naloxone", "enteric neurons", "damgo", "pathway", "mapk", "Chronic morphine treatment"], "article_id"=>1201159, "categories"=>["Biological Sciences"], "users"=>["Céline Duraffourd", "Erica Kumala", "Laura Anselmi", "Nicholas C. Brecha", "Catia Sternini"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0110230.g004", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Role_of_dynamin_on_MAPK_activation_in_enteric_neurons_/1201159", "title"=>"Role of dynamin on MAPK activation in enteric neurons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-10 03:49:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1713867"], "description"=>"<p>A: Single exposure to DAMGO (1 µM, 5 min) induced significant MAPK activation in naïve enteric neurons, whereas a second exposure to the same DAMGO dose following 2 hours DAMGO pretreatment abolished DAMGO-mediated MAPK response, indicating desensitization. B: Single exposure to DAMGO (1 µM) or morphine (10 µM) activated MAPK in chronic neurons. A second exposure to the same dose of DAMGO or morphine following 2 hours DAMGO or morphine pretreatment induced the same effect in chronic neurons as single exposures, indicating suppression of desensitization. (** p<0.01 vs. control in A and B). C and D: DAMGO and morphine inhibit forskolin-stimulated cAMP in naïve (C) and chronic (D) enteric neurons. This effect was not observed in naïve enteric neurons (C) with a second opioid stimulation following a prior 2 hour exposure, indicative of desensitization. D: Note the over 2 fold increase in cAMP in unstimulated chronic neurons (cAMP superactivation or “overshooting”) vs. naïve control; DAMGO and morphine inhibition of cAMP was not prevented by 2 hours DAMGO or morphine pretreatment in chronic neurons, indicating suppression of desensitization. **p<0.01 vs. controls. N = 5–7 experiments performed in duplicate per group.</p>", "links"=>[], "tags"=>["morphine treatment triggers changes", "activation", "Chronic Morphine Treatment Opioids", "Rat Enteric Neurons", "creb", "Chronic opioid treatment", "receptor antagonist naloxone", "enteric neurons", "damgo", "pathway", "mapk", "Chronic morphine treatment"], "article_id"=>1201160, "categories"=>["Biological Sciences"], "users"=>["Céline Duraffourd", "Erica Kumala", "Laura Anselmi", "Nicholas C. Brecha", "Catia Sternini"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0110230.g005", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Desensitization_of_956_OR_signaling_in_enteric_neurons_/1201160", "title"=>"Desensitization of μOR signaling in enteric neurons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-10 03:49:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1713865"], "description"=>"<p>DAMGO-induced MAPK activation in naive (A, C, E) and DAMGO- and morphine-activation of MAPK in chronic (B, D, F) enteric neurons. Naloxone (A, B), MEK1/2 inhibitor, U0126 (C, D) and hypertonic sucrose (E, F) prevented opioid induced MAPK activation in naïve (A, C, E) and chronic (B, D, F) neurons. **p<0.01 significantly different from control. N = 4–7 experiments in triplicate per group.</p>", "links"=>[], "tags"=>["morphine treatment triggers changes", "activation", "Chronic Morphine Treatment Opioids", "Rat Enteric Neurons", "creb", "Chronic opioid treatment", "receptor antagonist naloxone", "enteric neurons", "damgo", "pathway", "mapk", "Chronic morphine treatment"], "article_id"=>1201158, "categories"=>["Biological Sciences"], "users"=>["Céline Duraffourd", "Erica Kumala", "Laura Anselmi", "Nicholas C. Brecha", "Catia Sternini"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0110230.g003", "stats"=>{"downloads"=>0, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characterization_of_opioid_induced_MAPK_pathway_in_enteric_neurons_/1201158", "title"=>"Characterization of opioid-induced MAPK pathway in enteric neurons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-10 03:49:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1713869"], "description"=>"<p>Chronic morphine (MORPH) significantly delayed GI transit (reduction of geometric center) (**p<0.01 vs. control). MEK1/2 inhibitor alone (U0126) did not affect transit. Administration of MEK1/2 inhibitor together with morphine (MORPH+ U0126) reversed the delay in GI transit (**p<0.01 vs. MORPH). N = 5 per group.</p>", "links"=>[], "tags"=>["morphine treatment triggers changes", "activation", "Chronic Morphine Treatment Opioids", "Rat Enteric Neurons", "creb", "Chronic opioid treatment", "receptor antagonist naloxone", "enteric neurons", "damgo", "pathway", "mapk", "Chronic morphine treatment"], "article_id"=>1201162, "categories"=>["Biological Sciences"], "users"=>["Céline Duraffourd", "Erica Kumala", "Laura Anselmi", "Nicholas C. Brecha", "Catia Sternini"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0110230.g007", "stats"=>{"downloads"=>0, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_MEK1_2_inhibitor_U0126_on_GI_transit_delay_induced_by_chronic_morphine_in_rats_/1201162", "title"=>"Effect of MEK1/2 inhibitor (U0126) on GI transit delay induced by chronic morphine in rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-10 03:49:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1713864"], "description"=>"<p>DAMGO (1 µM, black bars) induced a transient MAPK/ERK1/2 activation in naïve (A) and chronic (B) neurons at 5 and 10 minutes, whereas morphine (grey bars) induced MAPK/ERK1/2 activation only in chronic (B) neurons. **p<0.01 compared to controls (white bars). N = 4–7 experiments in triplicate. Representative gels of pERK1/2 and tERK are shown at the bottom of each graph. tERK was used to verify that the treatment did not affect the total level of this protein and to confirm equal gel loading.</p>", "links"=>[], "tags"=>["morphine treatment triggers changes", "activation", "Chronic Morphine Treatment Opioids", "Rat Enteric Neurons", "creb", "Chronic opioid treatment", "receptor antagonist naloxone", "enteric neurons", "damgo", "pathway", "mapk", "Chronic morphine treatment"], "article_id"=>1201157, "categories"=>["Biological Sciences"], "users"=>["Céline Duraffourd", "Erica Kumala", "Laura Anselmi", "Nicholas C. Brecha", "Catia Sternini"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0110230.g002", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Opioid_induced_MAPK_activation_in_na_239_ve_A_and_chronically_treated_B_enteric_neurons_/1201157", "title"=>"Opioid-induced MAPK activation in naïve (A) and chronically treated (B) enteric neurons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-10 03:49:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/1713863"], "description"=>"<p>μOR immunoreactivity is at the cell surface in unstimulated and morphine-stimulated neurons (A, C arrows), and it is in the cytosol following stimulation with DAMGO (B) in naïve enteric neurons. μOR immunoreactivity is at the cell surface in unstimulated neurons (D, arrows), but in the cytosol following DAMGO or morphine stimulation (E, F) in chronic enteric neurons.</p>", "links"=>[], "tags"=>["morphine treatment triggers changes", "activation", "Chronic Morphine Treatment Opioids", "Rat Enteric Neurons", "creb", "Chronic opioid treatment", "receptor antagonist naloxone", "enteric neurons", "damgo", "pathway", "mapk", "Chronic morphine treatment"], "article_id"=>1201156, "categories"=>["Biological Sciences"], "users"=>["Céline Duraffourd", "Erica Kumala", "Laura Anselmi", "Nicholas C. Brecha", "Catia Sternini"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0110230.g001", "stats"=>{"downloads"=>0, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_956_OR_immunoreactivity_in_na_239_ve_enteric_neurons_A_8211_C_and_in_neurons_chronically_treated_with_morphine_D_8211_F_/1201156", "title"=>"μOR immunoreactivity in naïve enteric neurons (A–C) and in neurons chronically treated with morphine (D–F).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-10 03:49:05"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"15", "full-text"=>"14", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"13", "full-text"=>"15", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"32", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"26", "full-text"=>"29", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"27", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"14", "full-text"=>"15", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"21", "full-text"=>"33", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"15", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"28", "full-text"=>"31", "pdf"=>"25", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"22", "full-text"=>"27", "pdf"=>"20", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"23", "full-text"=>"43", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"22", "full-text"=>"26", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"26", "full-text"=>"26", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"21", "full-text"=>"21", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"37", "full-text"=>"35", "pdf"=>"17", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"28", "full-text"=>"25", "pdf"=>"21", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"29", "full-text"=>"32", "pdf"=>"16", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"22", "full-text"=>"22", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"2", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"24", "full-text"=>"19", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"14", "full-text"=>"10", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"16", "full-text"=>"20", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"21", "full-text"=>"15", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"10", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"10", "full-text"=>"13", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"16", "full-text"=>"12", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"6", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"5", "full-text"=>"9", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"15", "full-text"=>"16", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"2", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"12", "full-text"=>"13", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"13", "full-text"=>"14", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "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"=>"5", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"16", "full-text"=>"16", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"11", "full-text"=>"12", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"11", "full-text"=>"13", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"6", "full-text"=>"29", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"16", "full-text"=>"16", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"4", "full-text"=>"6", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"7", "full-text"=>"4", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"10", "full-text"=>"6", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}

Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[286]}, {"subject_area"=>"/Biology and life sciences/Neuroscience", "average_usage"=>[289]}, {"subject_area"=>"/Medicine and health sciences/Pain management", "average_usage"=>[277, 451]}]}
Loading … Spinner
There are currently no alerts