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

Nociceptin, nociceptin-(1–13)-NH2, Ac-RYYRWK-NH2, [Phe1ψ(CH2NH)Gly2]nociceptin-(1–13)-NH2, the new nociceptin analog [Nphe1]nociceptin-(1–13)-NH2, and endomorphin-1 have been tested in the isolated mouse colon. All peptides, except [Nphe1]nociceptin-(1–13)-NH2, caused concentration-dependent, tetrodotoxin-sensitive contractions showing similar maximal effects. Naloxone (1 μM) blocked the effect of endomorphin-1 but not that of the other peptides. [Nphe1]nociceptin-(1–13)-NH2 (10 μM) was inactive against endomorphin-1, but antagonized the contractile effects of nociceptin receptor ligands showing similar pA2 values (≈6.0). The present findings indicate that [Nphe1]nociceptin-(1–13)-NH2 is a low-potency, selective nociceptin receptor antagonist, devoid of residual agonist activity.