痛啡肽抑制豚鼠气道兴奋性非肾上腺素能非胆碱能反应

目的:研究痛啡肽(Nociceptin,NC)及U-50488H对豚鼠离体支气管环的非肾上腺素能非胆碱能兴奋(eNANC)所致收缩的抑制作用。方法:记录电场刺激及辣椒素引起标本eNANC反应的收缩张力,了解NC及U-50488H的作用。结果:NC 0.001-0.1μmol·L~(-1)可抑制标本的eNANC收缩。与对照组相比,NC 0.01μmol·L~(-1)抑制收缩达(43±31)％;预用纳洛酮0.1μmol·L~(-1)后,NC仍抑制收缩达(46±28)％。IC_(50)(95％可信限)是6.12(3.8-9.9)nmol·L~(-1)。U-50488H 0.01 -1μmol·L~(-1)可抑制eNANC收缩,其IC_(50)(95％可信限)为1.08(0.5-2.2)μmol·L~(-1),但是U-50488H 0.1μmol·L~(-1)的抑制作用可被纳洛酮0.1μmol·L~(-1)完全取消。辣椒素0.01-1μmol·L~(-1)可引起eNANC收缩,NC 0.01μmol·L~(-1)和U-50488H 0.1μmol·L~(-1)均不能明显影响辣椒素的作用。外源性神经激肽A 0.01μmol·L~(-1)引起的收缩不受NC和U-50488H 0.1μmol·L~(-1)的影响。结论:NC非纳洛酮敏感地抑制电场刺激引起的豚鼠气道eNANC反应;U-50488H通过激动阿片受体而抑制电场刺激引起的豚鼠气道eNANC反应。

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 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. CONCLUSION: 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.