[Nphe(1)]nociceptin-(1-13)-NH(2) antagonizes nociceptin effects in the mouse colon.
Nociceptin, nociceptin-(1-13)-NH(2), Ac-RYYRWK-NH(2), [Phe(1)psi(CH(2)&z.sbnd;NH)Gly(2)]nociceptin-(1-13)-NH(2), the new nociceptin analog [Nphe(1)]nociceptin-(1-13)-NH(2), and endomorphin-1 have been tested in the isolated mouse colon. All peptides, except [Nphe(1)]nociceptin-(1-13)-NH(2), caused concentration-dependent, tetrodotoxin-sensitive contractions showing similar maximal effects. Naloxone (1 microM) blocked the effect of endomorphin-1 but not that of the other peptides. [Nphe(1)]nociceptin-(1-13)-NH(2) (10 microM) was inactive against endomorphin-1, but antagonized the contractile effects of nociceptin receptor ligands showing similar pA(2) values (approximately 6.0). The present findings indicate that [Nphe(1)]nociceptin-(1-13)-NH(2) is a low-potency, selective nociceptin receptor antagonist, devoid of residual agonist activity.
Rizzi
A
A
Department of Experimental and Clinical Medicine, Section of Pharmacology, via Fossato Mortara, 17-19, Ferrara, Italy.
Bigoni
R
R
Caló
G
G
Guerrini
R
R
Salvadori
S
S
Regoli
D
D
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000819:agonists; D013779:Tetrodotoxin / Q000494:pharmacology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D002217:Carbachol; D009270:Naloxone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D013779:Tetrodotoxin; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C114149:nociceptin (1-13)-NH2, Phe(1)-psi(CH2-NH)-Gly(2)-; C403776:nociceptin-(1-13)-NH2, NPhe(1)-; C000722287:Oprl1 protein, mouse