[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.