[Nphe(1)]nociceptin-(1-13)-NH2 antagonizes nociceptin effects in the mousecolon

Nociceptin, nociceptin-(1-13)-NH2, Ac-RYYRWK-NH2, [Phe(1)psi(CH2-NH)Gly(2)] nociceptin-(1-13)-NH2, the new nociceptin analog [Nphe(1)]nociceptin-(1-13) -NH2, and endomorphin-1 have been tested in the isolated mouse colon. All p eptides, except [Nphe(1)]nociceptin-(1-13)-NH2, caused concentration-depend ent, tetrodotoxin-sensitive contractions showing similar maximal effects. N aloxone (1 mu M) blocked the effect of endomorphin-1 but not that of the ot her peptides. [Nphe(1)]nociceptin-(1-13)-NH2 (10 mu M) was inactive against endomorphin-1, but antagonized the contractile effects of nociceptin recep tor ligands showing similar pA(2) values (approximate to 6.0). The present findings indicate that [Nphe(1)]nociceptin-(1-13)-NH2 is a low-potency, sel ective nociceptin receptor antagonist, devoid of residual agonist activity. (C) 1999 Elsevier Science B.V. All rights reserved.