脑啡肽酶抑制剂增强神经肽对人支气管的收缩作用。

Potentiation of the contractile effects of neuropeptides in human bronchus by an enkephalinase inhibitor.

作者信息

Black J L, Johnson P R, Armour C L

机构信息

Department of Pharmacology, University of Sydney, NSW Australia.

出版信息

Pulm Pharmacol. 1988;1(1):21-3. doi: 10.1016/0952-0600(88)90006-3.

DOI:10.1016/0952-0600(88)90006-3

PMID:2980283

Abstract

Many neuropeptides have been identified in human airways and these are susceptible to breakdown by endogenous enkephalinases. This study investigated the effect of enkephalinase inhibition with phosphoramidon (10(-5) M) on contractile responses to neurokinin A, eledoisin, physalaemin and substance P in human isolated bronchial smooth muscle. Contractile responses to the maximal doses of neuropeptides given were potentiated by phosphoramidon, whereas those to carbachol were unaffected. In addition, neuropeptide response curves were significantly (P less than 0.05) shifted to the left as measured by geometric mean dose ratios (95% confidence intervals) of 20.9 (5.4-81.3) n = 7 for neurokinin A; 63 (21.8-181.9) n = 6 for eledoisin, 44.7 (3.2-616.6) n = 5 for physalaemin and 6.9 (2.4-20) n = 6 for substance P. We conclude that enkephalinase inhibition in vitro significantly potentiates the contractile response to neuropeptides in human airway smooth muscle. Absence of, or decreased activity of enkephalinase could lead to enhanced effects of endogenous neuropeptides in human airways in vivo.

摘要

许多神经肽已在人类气道中被鉴定出来，并且它们易被内源性脑啡肽酶分解。本研究调查了用磷酰胺（10⁻⁵ M）抑制脑啡肽酶对人离体支气管平滑肌中对神经激肽A、eledoisin、雨蛙肽和P物质的收缩反应的影响。磷酰胺增强了对所给最大剂量神经肽的收缩反应，而对卡巴胆碱的收缩反应则无影响。此外，通过几何平均剂量比（95%置信区间）测量，神经肽反应曲线显著（P<0.05）左移，神经激肽A为20.9（5.4 - 81.3），n = 7；eledoisin为63（21.8 - 181.9），n = 6；雨蛙肽为44.7（3.2 - 616.6），n = 5；P物质为6.9（2.4 - 20），n = 6。我们得出结论，体外抑制脑啡肽酶可显著增强人气道平滑肌对神经肽的收缩反应。脑啡肽酶的缺失或活性降低可能导致体内内源性神经肽在人类气道中的作用增强。