Effect of SR-140333,a neurokinin-1 receptor antagonist,on airway reactivity to methacholine in sedated rats

目的：探讨神经激肽对乙酰甲胆碱（ＭＣ）气道反应性的作用．方法：观察非肽类ＮＫ１受体拮抗剂ＳＲ１４０３３３对镇静大鼠的ＭＣ气道反应性和离体气管条的收缩反应．结果：ＳＲ１４０３３３抑制ＭＣ气雾（１０－１０００μｍｏｌ／ｍ３）引起的呼吸频率增快，抑制ＭＣ气雾（１ｍｍｏｌ／ｍ３）反应的ＩＤ５０为４９（１４－１７２μｇ·ｋｇ－１）；ＳＲ１４０３３３１μｍｏｌ·Ｌ－１对乙酰甲胆碱引起的气管平滑肌收缩无抑制作用．阿托品可阻断ＭＣ的在体和离体反应．结论：内源性速激肽参与在体ＭＣ气道反应，至少部分由ＮＫ１受体介导．

IM: To study the roles of neurokinins in the airway reactivity (AR) to methacholine chloride (MC). METHODS: The effects of ( S ) 1 (2 [3,4 di-chlorophenyl) 1 (3 isopropoxyphenylacetyl)piperidin 3 yl]ethyl) 4 phenyl 1 azoniabicyclo octane·chloride (SR 140333), a neurokinin 1 receptor antagonist, on AR to inhaled MC in diazepam sedated rats, and on MC induced contraction of isolated tracheal spiral strips were observed. RESULTS: SR 140333 inhibited the increase in respiratory rate (RR) induced by MC aerosol (10-1000 μmol/m 3), and the ID 50 for inhibiting the response to MC aerosol (1 mmol/m 3) was 4 9 μg·kg -1 (95 % confidence limits 1 4-17 2 μg·kg -1 ). SR 140333 1 μmol·L -1 had no inhibitory effect on MC induced tracheal contraction. Atropine blocked responses to MC both in vivo and in vitro . CONCLUSION: Endogenous neurokinins are involved in the AR to MC in rats, at least partly mediated via neurokinin 1 receptors.