{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T17:20:30Z","timestamp":1777569630606,"version":"3.51.4"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DA025574"],"award-info":[{"award-number":["DA025574"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Stimulation of nociceptin\/orphanin FQ peptide (NOP) opioid receptors by the endogenous ligand nociceptin (Noc) leads to voltage\u2010gated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel inhibition or G protein inwardly rectifying K\n                    <jats:sup>+<\/jats:sup>\n                    channel activation. One mechanism of G protein\u2010coupled receptor (GPCR) desensitization occurs when G protein\u2010coupled receptor kinases (GRK) phosphorylate the agonist\u2010bound receptors. In the continued presence of an agonist, G\u03b2\u03b3 recruits GRK to the plasma membrane where GPCR are then phosphorylated by GRK. The purpose of this study was to identify the GRK subtype responsible for desensitization of the Noc\u2010mediated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    current inhibition in rat stellate ganglion (SG) neurons. We observed that GRK2 and GRK5 are expressed in SG neurons. Further, silencing either GRK subtype alone or together employing siRNA did not overtly alter their Noc pharmacological profile. We assessed NOP receptor desensitization employing a protocol where the peak Ca\n                    <jats:sup>2+<\/jats:sup>\n                    current inhibition was measured during intermittent application of high Noc concentrations in the continued presence of the IC\n                    <jats:sub>50<\/jats:sub>\n                    Noc concentration. With this approach, we observed complete Ca\n                    <jats:sup>2+<\/jats:sup>\n                    current desensitization in neurons transfected with either scrambled or GRK2 siRNA following exposure to high Noc concentrations. On the other hand, full desensitization of the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    currents was not observed in neurons in which GRK5 was silenced alone or with GRK2. That is, coupling of NOP receptors with Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels was still observed following application of high Noc concentration. These results suggest that GRK5 plays a key role in the mechanism that mediates NOP receptor desensitization in SG neurons.\n                  <\/jats:p>","DOI":"10.1002\/jnr.70110","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T07:53:15Z","timestamp":1768377195000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["G Protein\u2010Coupled Receptor Kinase 5 (\n                    <scp>GRK5<\/scp>\n                    ) Modulates Nociceptin\/Orphanin\n                    <scp>FQ<\/scp>\n                    Opioid (\n                    <scp>NOP<\/scp>\n                    ) Receptor Desensitization in Rat Sympathetic Neurons"],"prefix":"10.1002","volume":"104","author":[{"given":"Mohamed","family":"Farrag","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine Penn State College of Medicine  Hershey Pennsylvania 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