Enkephalinase inhibitor potentiates substance P- and electrically induced contraction in ferret trachea.
Enkephalinase inhibitor potentiates substance P- and electrically induced contraction in ferret trachea.
复制标题
脑啡肽酶抑制剂可增强 P 物质和电诱导的雪貂气管收缩。
DOI：
10.1152/jappl.1987.63.4.1401
复制
发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Borson,DB
中科院分区：
文献类型：
--
作者：
Sekizawa,K;Tamaoki,J;Nadel,JA;Borson,DB
为了确定内源性脑啡肽酶（EC 3.4.24.11）在调节肽诱导的气道平滑肌收缩中的作用，我们研究了脑啡肽酶抑制剂亮氨酸-硫啡烷（Leu-thiorphan）对离体雪貂气管平滑肌段对P物质（SP）和电场刺激（EFS）的反应的影响。Leu-thiorphan将SP的剂量-反应曲线移至较低浓度。阿托品或SP拮抗剂[D-Pro 2，D-Trp 7，9]SP在Leu-thiorphan存在下显著抑制SP诱导的收缩。Leu-thiorphan剂量依赖性地增加对EFS的收缩反应，该作用被SP拮抗剂[D-Pro 2，D-Trp 7，9] SP显著抑制。在不引起收缩的浓度下，SP增加对EFS的收缩反应。这种作用增强亮硫啡烷剂量依赖性，并不抑制六甲双铵或酚妥拉明，但抑制阿托品。由于收缩反应的乙酰胆碱没有显着影响SP或Leu-thiorphan，SP的增强作用可能是对突触前-节后胆碱能神经传递。卡托普利，bestatin，或leupeptin没有增加收缩，这表明脑啡肽酶的影响负责。这些结果表明，内源性速激肽调节平滑肌收缩和内源性脑啡肽酶调节收缩产生的内源性或外源性速激肽和速激肽诱导的胆碱能神经传递的便利。
To determine the role of endogenous enkephalinase (EC 3.4.24.11) in regulating peptide-induced contraction of airway smooth muscle, we studied the effect of the enkephalinase inhibitor, leucine-thiorphan (Leu-thiorphan), on responses of isolated ferret tracheal smooth muscle segments to substance P (SP) and to electrical field stimulation (EFS). Leu-thiorphan shifted the dose-response curve to SP to lower concentrations. Atropine or the SP antagonist [D-Pro2,D-Trp7,9]SP significantly inhibited SP-induced contractions in the presence of Leu-thiorphan. Leu-thiorphan increased the contractile responses to EFS dose dependently, an effect that was significantly inhibited by the SP antagonist [D-Pro2,D-Trp7,9]SP. SP, in a concentration that did not cause contraction, increased the contractile responses to EFS. This effect was augmented by Leu-thiorphan dose dependently and was not inhibited by hexamethonium or by phentolamine but was inhibited by atropine. Because contractile responses to acetylcholine were not significantly affected by SP or by Leu-thiorphan, the potentiating effects of SP were probably on presynaptic-postganglionic cholinergic neurotransmission. Captopril, bestatin, or leupeptin did not augment contractions, suggesting that enkephalinase was responsible for the effects. These results suggest that endogenous tachykinins modulate smooth muscle contraction and endogenous enkephalinase modulates contractions produced by endogenous or exogenous tachykinins and tachykinin-induced facilitation of cholinergic neurotransmission.