NOCICEPTIN INHIBITS NONADRENERGIC NONCHOLINERGIC CONTRACTION IN GUINEA-PIG AIRWAY

1 Electrical field stimulation (EFS) of guinea-pig isolated main bronc hi induced a non-adrenergic noncholinergic (NANC) contractile response . Nociceptin (0.01-1 mu M) significantly inhibited the contractile res ponse to EFS (P<0.01), but nut to capsaicin (P>0.05). 2 The mu-, delta - and kappa-opioid receptor antagonists, naloxone (0.3 mu M), naltrind ole (3 mu M) and norbinaltorphimine (1 mu M), respectively, did not si gnificantly affect the inhibitory effect of nociceptin (0.03 mu M; P<0 .05). 3 The novel nociceptin antagonist, [Phe(1)Psi(CH2-NH)Gly(2)]noci ceptin(1-13)NH2 (0.03-1 mu M): the sigma ligands, carbetapentane (30 m u M), 3-phenylpiperidine (30-100 mu M) and (+)-cyclazocine (10-100 mu M) significantly reversed the inhibitory effect of nociceptin (0.03 mu M, P <0.05). In contrast, rimcazole, did not significantly reverse th e inhibitory effect of nociceptin (0.03 mu M) at any concentration tes ted (P>0.05). 4 EFS of guinea-pig bronchial preparations significantly increased SP-LI release above basal SP-LI (P<0.05). In the presence o f nociceptin (1 mu M), EFS induced a significant increase in SP-LI rel ease above basal SP-LI release (P<0.05). Nociceptin caused a 59+/-11% (n=5) inhibition of EFS-induced release of SP-LI. 5 Nociceptin reduces the release of sensory neuropeptides induced by EFS, but not capsaici n, from guinea-pig airways. These experiments provide further evidence for a role for nociceptin in regulating the release of sensory neurop eptides in response to EFS.