Antagonistic effects of [Nphe1]nociceptin(1-13)NH2 on nociceptin receptor mediated inhibition of cAMP formation in Chinese hamster ovary cells stably expressing the recombinant human nociceptin receptor.
Nociceptin/orphanin FQ (NC) is the endogenous ligand for the nociceptin receptor (NCR) which is negatively coupled to adenylyl cyclase to inhibit the formation of cAMP. In this study we describe the inhibitory action of the novel NC analogue, [Nphe1]nociceptin(1-13)NH2 on cAMP formation in Chinese hamster ovary cells expressing the human NCR. NC, NC(1-13)NH2, the pseudopeptides [Phe1psi(CH2-NH)Gly2]NC(1-17)NH2 and [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2, the hexapeptide, acetyl-Arg-Tyr-Tyr-Arg-Trp-Lys-NH2 and buprenorphine all produced a concentration dependent inhibition of forskolin stimulated cAMP formation. This inhibition was competitively reversed by [Nphe1]NC(1-13)NH2 with essentially identical pA2 values (6.12-6.48). [Nphe1]NC(1-13)NH2 showed per se a negligible residual agonist activity (alpha < 0.15).
Hashimoto
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Y
University Department of Anaesthesia and Pain Management, Leicester Royal Infirmary, UK.
Caló
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Guerrini
R
R
Smith
G
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Lambert
D G
DG
D000818:Animals; D001667:Binding, Competitive; D002047:Buprenorphine / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000096:biosynthesis*; D006801:Humans; D015394:Molecular Structure; D009292:Narcotic Antagonists; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D018847:Opioid Peptides / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000819:agonists / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D000094942:Nociceptin Receptor
C404152:CAM 6369; D009292:Narcotic Antagonists; D009842:Oligopeptides; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D011993:Recombinant Fusion Proteins; C114149:nociceptin (1-13)-NH2, Phe(1)-psi(CH2-NH)-Gly(2)-; C404153:nociceptin (1-17)-NH2, Phe(1)-psi(CH2NH)-Gly(2)-; C403776:nociceptin-(1-13)-NH2, NPhe(1)-; D002047:Buprenorphine; D000242:Cyclic AMP; D000094942:Nociceptin Receptor