title: Agonist-regulated endocytosis and desensitization of the human nociceptin receptor.
abstract: A series of nociceptin receptor ligands has been investigated in relationship to their capability to promote receptor endocytosis, desensitization (evaluated as inhibition of forskolin-stimulated cAMP production) and compensatory upregulation of adenylyl cyclase activity in CHO-K1 cells expressing the cloned human nociceptin receptor. Nociceptin (NC), [Arg14, Lys15]NC-NH2 and NNC 63-0532 (0.01 nM-10 microM) induce a concentration-dependent endocytosis and recycling of the nociceptin receptor. This mechanism contributes to maintain receptor signaling as it counteracts desensitization development and enhances a compensatory upregulation of adenyl cyclase activity. In contrast, the partial agonists [Phe1,Psi(CH2NH)Gly2]NC(1-13)-NH2, Ac-RYYRIK-NH2 and Ac-RYYRWK-NH2 (up to 100 microM) fail to induce receptor endocytosis and cause a pronounced receptor desensitization that is not influenced by monensin, a blocker of recycling of the internalized receptors.
authors.affiliation: Department of Pharmacology, University of Bologna, Bologna, Italy. santi.spampinato@unibo.it
authors.forename: Santi
authors.initials: S
authors.lastname: Spampinato
authors.forename: Monica
authors.initials: M
authors.lastname: Baiula
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004705:Endocytosis / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D008985:Monensin / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011957:Receptors, Opioid / Q000819:agonists* / Q000378:metabolism / Q000502:physiology*; D000094942:Nociceptin Receptor
chemical_list: D000701:Analgesics, Opioid; D007476:Ionophores; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D005576:Colforsin; D008985:Monensin; D000242:Cyclic AMP; D000094942:Nociceptin Receptor