Inhibition by nociceptin on excitatory non-adrenergic non-cholinergic response in guinea pig airways

AIM: To study the effect of nociceptin (NC), a newly discovered heptadecape ptide, and U-50488H, a kappa-opioid receptor agonist, on excitatory non-adr energic noncholinergic (eNANC) constriction responses in guinea pig isolate d bronchus. METHODS: An eNANC response was induced by electric field stimul ation (EFS) in the preparation via activation of the sensory nerve terminal s. The effect of NC and U-50488H was analyzed on the response. RESULTS: Noc iceptin 0.001 - 0.1 mu mol L-l inhibited the eNANC constriction which was i nduced by EFS but not by capsaicin in guinea pig bronchus. The constriction inhibited by NC 0.01 mu mol .L-1 was (43 +/- 31) % compared with the contr ol. After pretreatment with naloxone 0.1 mu mol L-l, the constriction was i nhibited by (46 +/- 28) %, without marked change compared with the above fi gure. IC50 (95 % Of confidence Limits) was 6.12 (3.8 - 9.9) nmol .L-1. U-50 488H also inhibited the EFS-evoked eNANC constriction and the effect was ab olished after pretreatment with naloxone. IC50(95 % of confidence limits) w as 1.08 (0.5 -2.2) mu mol .L-1. Capsaicin 0.01-1 mu mol .L-1 caused a cumul ative constriction response in the preparation. Moreover, the effect of cap saicin was not affected by pretreatment with NC 0.01 mu mol .L-1 or U-50488 H 0.1 mu mol .L-1. The constriction induced by exogenous neurokinin A, were also unaffected by treatment with NC 0.01 mu mol .L-1 or U-50488H 0.1 mu m ol .L-1 in isolated bronchus. CONCLUSION: Nociceptin inhibits EFS-induced e NANC constriction, which is not reversed by naloxone, while U-50488H inhibi ts EFS-induced eNANC response via acitivation of opioid receptor in guinea pig airways.