Nociceptin inhibits capsaicin-sensitive contraction to mesenteric nerve stimulation in the guinea-pig isolated ileum

Mesenteric nerve stimulation (MNS) in the presence of guanethidine and hexamethonium antidromically stimulated extrinsic sensory nerve fibers and cholinergic myenteric motor neurons, resulting in longitudinal muscle contraction in the isolated guinea-pig ileum. Nociceptin (NC) is a recently discovered neuropeptide that structurally resembles an opioid peptide. The aim of the current study was to examine how NC affects the contractile responses to MNS in the isolated guinea-pig ileum, in comparison with an opiate, methionine–enkephalin. These contractions were auxotonically recorded and their amplitude was analyzed. NC (1–100 nM) and methionine–enkephalin (0.1–10 μM) concentration-dependently inhibited the response to MNS (20 Hz, 0.5 ms, supramaximal currents). Naloxone (10 μM) significantly diminished the inhibitory effect of methionine–enkephalin (0.1–10 μM), but did not antagonize the inhibitory effect of NC (1–100 nM). We conclude that NC receptors, distinct from opioid receptors, exist on the capsaicin-sensitive sensory nerve fibers and/or myenteric cholinergic motor neurons in the guinea-pig ileum and that specific antagonists for these NC receptors are not found yet.