Fang L B, Wu Y, Zhang L F, Fang W Q
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310006, China.
Acta Pharmacol Sin. 2001 Jun;22(6):561-5.
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.
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.
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.
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.
研究新发现的十七肽孤啡肽（NC）和κ-阿片受体激动剂U-50488H对豚鼠离体支气管兴奋性非肾上腺素能非胆碱能（eNANC）收缩反应的影响。
通过激活感觉神经末梢，在制备物中采用电场刺激（EFS）诱导eNANC反应。分析NC和U-50488H对该反应的影响。
0.001 - 0.1微摩尔/升的孤啡肽抑制豚鼠支气管中由EFS而非辣椒素诱导的eNANC收缩。与对照组相比，0.01微摩尔/升的孤啡肽抑制的收缩为（43±31）%。用0.1微摩尔/升纳洛酮预处理后，收缩被抑制（46±28）%，与上述数据相比无明显变化。半数抑制浓度（IC50，95%置信限）为6.12（3.8 - 9.9）纳摩尔/升。U-50488H也抑制EFS诱发的eNANC收缩，且在用纳洛酮预处理后该作用被消除。IC50（95%置信限）为1.08（0.5 - 2.2）微摩尔/升。0.01 - 1微摩尔/升的辣椒素在制备物中引起累积收缩反应。此外，辣椒素的作用不受0.01微摩尔/升的孤啡肽或0.1微摩尔/升的U-50488H预处理的影响。在离体支气管中，外源性神经激肽A诱导的收缩也不受0.01微摩尔/升的孤啡肽或0.1微摩尔/升的U-50488H处理的影响。
孤啡肽抑制EFS诱导的eNANC收缩，且该作用不被纳洛酮逆转，而U-50488H通过激活豚鼠气道中的阿片受体抑制EFS诱导的eNANC反应。
