Nociceptin inhibits non-adrenergic non-cholinergic contraction in guinea-pig airway.
1. Electrical field stimulation (EFS) of guinea-pig isolated main bronchi induced a non-adrenergic non-cholinergic (NANC) contractile response. Nociceptin (0.01-1 microm) significantly inhibited the contractile response to EFS (P<0.01), but not to capsaicin (P>0.05). 2. The mu-, delta- and kappa-opioid receptor antagonists, naloxone (0.3 microM), naltrindole (3 microM) and norbinaltorphimine (1 microm), respectively, did not significantly affect the inhibitory effect of nociceptin (0.03 microM; P>0.05). 3. The novel nociceptin antagonist, [Phe1psi(CH2-NH)Gly2]nociceptin(1-13)NH2 (0.03-1 microM); the sigma ligands, carbetapentane (30 microM), 3-phenylpiperidine (30-100 microM) and (+)-cyclazocine (10-100 microM) significantly reversed the inhibitory effect of nociceptin (0.03 microM, P<0.05). In contrast, rimcazole, did not significantly reverse the inhibitory effect of nociceptin (0.03 microM) at any concentration tested (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 of nociceptin (1 microM), EFS induced a significant increase in SP-LI release 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 capsaicin, from guinea-pig airways. These experiments provide further evidence for a role for nociceptin in regulating the release of sensory neuropeptides in response to EFS.
Shah
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Sackler Institute of Pulmonary Pharmacology, Department of Respiratory Medicine, King's College School of Medicine and Dentistry, London.
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D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism*; D018847:Opioid Peptides / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000819:agonists*; D013373:Substance P / Q000187:drug effects / Q000378:metabolism; D000097629:Nociceptin
D002211:Capsaicin; D009479:Neuropeptides; D018847:Opioid Peptides; D011957:Receptors, Opioid; D013373:Substance P; D000097629:Nociceptin