毒蕈碱M1受体刺激牛脑动脉中的磷酸肌醇水解。

Muscarinic M1 receptors stimulate phosphoinositide hydrolysis in bovine cerebral arteries.

作者信息

Garcia-Villalon A L, Ehlert F J, Krause D N, Duckles S P

机构信息

Department of Pharmacology, College of Medicine, University of California, Irvine 92717.

出版信息

Life Sci. 1990;47(23):2163-9. doi: 10.1016/0024-3205(90)90316-j.

DOI:10.1016/0024-3205(90)90316-j

PMID:2176261

Abstract

The muscarinic agonist oxotremorine-M produced a concentration-dependent increase in phosphoinositide hydrolysis in bovine pial arteries. The maximal effect was 5.9 +/- 0.89 fold over basal levels, and the EC50 for oxotremorine-M was 8.9 x 10(-6) M. The phosphoinositide response in arteries with the luminal endothelium removed was similar to the response in intact arteries. The specific muscarinic antagonists pirenzepine, 4-DAMP and methoctramine produced parallel shifts of the concentration-response curve to oxotremorine-M, with the following order of potency (pKB): 4-DAMP (8.59 +/- 0.10) greater than pirenzepine (8.12 +/- 0.11) greater than methoctramine (6.77 +/- 0.20). These results indicate that muscarinic stimulation activates phosphoinositide hydrolysis in cerebral arteries, and that the muscarinic receptors mediating this increase are similar to the M1 subtype.

摘要

毒蕈碱激动剂氧化震颤素-M可使牛软脑膜动脉中的磷酸肌醇水解呈浓度依赖性增加。最大效应比基础水平高5.9±0.89倍，氧化震颤素-M的EC50为8.9×10(-6)M。去除管腔内皮层的动脉中的磷酸肌醇反应与完整动脉中的反应相似。特异性毒蕈碱拮抗剂哌仑西平、4-二甲基氨基吡啶（4-DAMP）和甲溴东莨菪碱使氧化震颤素-M的浓度-反应曲线平行右移，效价顺序如下（pKB）：4-DAMP（8.59±0.10）＞哌仑西平（8.12±0.11）＞甲溴东莨菪碱（6.77±0.20）。这些结果表明，毒蕈碱刺激可激活脑动脉中的磷酸肌醇水解，介导这种增加的毒蕈碱受体类似于M1亚型。