Y-27632增强β2-肾上腺素能受体激动剂对牛气管平滑肌的舒张作用。

Y-27632 potentiates relaxant effects of beta 2-adrenoceptor agonists in bovine tracheal smooth muscle.

作者信息

Nakahara T, Moriuchi H, Yunoki M, Sakamato K, Ishii K

机构信息

Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo, Japan.

出版信息

Eur J Pharmacol. 2000 Feb 11;389(1):103-6. doi: 10.1016/s0014-2999(99)00891-2.

DOI:10.1016/s0014-2999(99)00891-2

PMID:10686302

Abstract

We examined how (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide (Y-27632), an inhibitor of Rho-associated coiled coil-forming protein kinase (ROCK I) and Rho kinase (ROCK II), affects the relaxant responses to beta(2)-adrenoceptor agonists in bovine tracheal smooth muscle preparations precontracted with methacholine. Y-27632 (0.3-30 microM) caused a concentration-dependent attenuation of precontraction with methacholine (0.3-3 microM). Pretreatment with Y-27632 (1 microM) significantly (P<0.05) augmented salbutamol (0.3-100 nM) and terbutaline (0.3 nM-1 microM)-induced relaxations. These results suggest that the ROCK inhibitor could become a new type bronchodilator and its combination with beta(2)-adrenoceptor agonists may become a novel strategy for the long-term treatment of asthma.

摘要

我们研究了Rho相关卷曲螺旋形成蛋白激酶（ROCK I）和Rho激酶（ROCK II）的抑制剂（+）-（R）-反式-4-（1-氨基乙基）-N-（4-吡啶基）环己烷甲酰胺（Y-27632）如何影响在经乙酰甲胆碱预收缩的牛气管平滑肌制剂中对β2-肾上腺素能受体激动剂的舒张反应。Y-27632（0.3 - 30微摩尔）引起了与乙酰甲胆碱（0.3 - 3微摩尔）预收缩的浓度依赖性减弱。用Y-27632（1微摩尔）预处理显著（P<0.05）增强了沙丁胺醇（0.3 - 100纳摩尔）和特布他林（0.3纳摩尔 - 1微摩尔）诱导的舒张。这些结果表明，ROCK抑制剂可能成为一种新型支气管扩张剂，并且其与β2-肾上腺素能受体激动剂的联合可能成为哮喘长期治疗的新策略。