Nociceptin inhibits tonic nitric oxide release in the mouse isolated proximal colon

Nociceptin/orphanin FQ, the endogenous ligand of the opioid receptor-like ( ORL1) receptor, caused contractions in the isolated colon of the mouse. Tet rodotoxin and the nitric oxide (NO) synthase inhibitor N omega-nitro-L-argi nine also produced contractions which were quantitatively similar to those seen in response to nociceptin. In the presence of either tetrodotoxin or N omega-nitro-L-arginine, nociceptin was unable to cause a further contracti on, whereas the muscarinic receptor agonist carbachol elicited a contractil e response. Nociceptin had no contractile activity in colonic preparations contracted by No-nitro-L-arginine then relaxed by addition of the NO donor sodium nitroprusside. These data suggest that nociceptin causes contraction s of the mouse proximal colon by inhibiting the tonic, neuronal release of NO. (C) 2000 Elsevier Science B.V. All rights reserved.