Inhibition by nociceptin on excitatory non-adrenergic non-cholinergic response in guinea pig airways.
OBJECTIVE
To study the effect of nociceptin (NC), a newly discovered heptadecapeptide, and U-50488H, a kappa-opioid receptor agonist, on excitatory non-adrenergic non-cholinergic (eNANC) constriction responses in guinea pig isolated bronchus.


METHODS
An eNANC response was induced by electric field stimulation (EFS) in the preparation via activation of the sensory nerve terminals. The effect of NC and U-50488H was analyzed on the response.


RESULTS
Nociceptin 0.001 - 0.1 micromol/L inhibited the eNANC constriction which was induced by EFS but not by capsaicin in guinea pig bronchus. The constriction inhibited by NC 0.01 micromol/L was (43 +/- 31) % compared with the control. After pretreatment with naloxone 0.1 micromol/L, the constriction was inhibited by (46 +/- 28) %, without marked change compared with the above figure. IC50 (95 % of confidence limits) was 6.12 (3.8 - 9.9) nmol/L. U-50488H also inhibited the EFS-evoked eNANC constriction and the effect was abolished after pretreatment with naloxone. IC50 (95 % of confidence limits) was 1.08 (0.5 - 2.2) micromol/L. Capsaicin 0.01 - 1 micromol/L caused a cumulative constriction response in the preparation. Moreover, the effect of capsaicin was not affected by pretreatment with NC 0.01 micromol/L or U-50488H 0.1 micromol/L. The constriction induced by exogenous neurokinin A, were also unaffected by treatment with NC 0.01 micromol/L or U-50488H 0.1 micromol/L in isolated bronchus.


CONCLUSIONS
Nociceptin inhibits EFS-induced eNANC constriction, which is not reversed by naloxone, while U-50488H inhibits EFS-induced eNANC response via activation of opioid receptor in guinea pig airways.
Fang
L B
LB
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310006, China. fanglb@zjuem.zju.edu.cn
Wu
Y
Y
Zhang
L F
LF
Fang
W Q
WQ
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D016084:Bronchoconstriction / Q000187:drug effects*; D004558:Electric Stimulation; D018846:Excitatory Amino Acids / Q000819:agonists; D006168:Guinea Pigs; D066298:In Vitro Techniques; D018847:Opioid Peptides / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000819:agonists; D014665:Vasodilator Agents / Q000494:pharmacology*; D000097629:Nociceptin
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D018846:Excitatory Amino Acids; D018847:Opioid Peptides; D017473:Receptors, Opioid, kappa; D014665:Vasodilator Agents; D000097629:Nociceptin