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. Tetrodotoxin and the nitric oxide (NO) synthase inhibitor Nomega-nitro-L-arginine also produced contractions which were quantitatively similar to those seen in response to nociceptin. In the presence of either tetrodotoxin or Nomega-nitro-L-arginine, nociceptin was unable to cause a further contraction, whereas the muscarinic receptor agonist carbachol elicited a contractile response. Nociceptin had no contractile activity in colonic preparations contracted by Nomega-nitro-L-arginine then relaxed by addition of the NO donor sodium nitroprusside. These data suggest that nociceptin causes contractions of the mouse proximal colon by inhibiting the tonic, neuronal release of NO.