{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:10:04Z","timestamp":1788869404823,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["DA08163"],"award-info":[{"award-number":["DA08163"]}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      This study examined the role of agents known to activate\n                      <jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content>\n                      on morphine\u2010induced desensitization of \u03bc\u2010opioid receptors (\n                      <jats:styled-content style=\"fixed-case\">MOP<\/jats:styled-content>\n                      receptors) in brain slices containing locus coeruleus neurons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Intracellular recordings were obtained from rat locus coeruleus neurons. Two measurements were used to characterize desensitization, the decline in hyperpolarization induced by application of a saturating concentration of agonist (acute desensitization) and the decrease in hyperpolarization induced by a subsaturating concentration of [\n                      <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>\n                      et]\n                      <jats:sup>5<\/jats:sup>\n                      enkephalin (\n                      <jats:styled-content style=\"fixed-case\">ME<\/jats:styled-content>\n                      ) following washout of the saturating concentration (sustained desensitization). Internalization of\n                      <jats:styled-content style=\"fixed-case\">MOP<\/jats:styled-content>\n                      receptors was studied in brain slices prepared from transgenic mice expressing\n                      <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>\n                      lag\u2010\n                      <jats:styled-content style=\"fixed-case\">MOP<\/jats:styled-content>\n                      receptors. The subcellular distribution of activated\n                      <jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content>\n                      was examined using a novel fluorescent sensor of\n                      <jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content>\n                      in\n                      <jats:styled-content style=\"fixed-case\">HEK<\/jats:styled-content>\n                      293 cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      The phorbol esters (PMA and PDBu) and muscarine increased acute desensitization induced by a saturating concentration of morphine and\n                      <jats:styled-content style=\"fixed-case\">ME<\/jats:styled-content>\n                      . These effects were not sensitive to staurosporine. Staurosporine did not block the decline in hyperpolarization induced by muscarine. PDBu and muscarine did not affect sustained desensitization induced by\n                      <jats:styled-content style=\"fixed-case\">ME<\/jats:styled-content>\n                      nor did phorbol esters or muscarine change the trafficking of\n                      <jats:styled-content style=\"fixed-case\">MOP<\/jats:styled-content>\n                      receptors induced by morphine or\n                      <jats:styled-content style=\"fixed-case\">ME<\/jats:styled-content>\n                      . The distribution of activated\n                      <jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content>\n                      measured in\n                      <jats:styled-content style=\"fixed-case\">HEK<\/jats:styled-content>\n                      293 cells differed depending on which phorbol ester was applied.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>\n                      This study demonstrates a distinct difference in two measurements that are often used to evaluate desensitization. The measure of decline correlated well with the reduction in peak amplitudes caused by\n                      <jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content>\n                      activators implicating the modification of other factors rather than\n                      <jats:styled-content style=\"fixed-case\">MOP<\/jats:styled-content>\n                      receptors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Linked Articles<\/jats:title>\n                    <jats:p>\n                      This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/dx.doi.org\/10.1111\/bph.2015.172.issue-2\">http:\/\/dx.doi.org\/10.1111\/bph.2015.172.issue-2<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.12712","type":"journal-article","created":{"date-parts":[[2014,4,4]],"date-time":"2014-04-04T03:13:23Z","timestamp":1396581203000},"page":"583-592","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Does\n                    <scp>PKC<\/scp>\n                    activation increase the homologous desensitization of \u03bc opioid receptors?"],"prefix":"10.1111","volume":"172","author":[{"given":"Seksiri","family":"Arttamangkul","sequence":"first","affiliation":[{"name":"Vollum Institute Oregon Health and Science University Portland OR 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