Honda K, Takano Y, Kamiya H
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan.
Jpn J Pharmacol. 1993 May;62(1):43-7. doi: 10.1254/jjp.62.43.
We have examined the pharmacological subtypes of muscarinic receptors mediating phosphoinositide hydrolysis and contraction in the longitudinal smooth muscle of guinea pig ileum with the use of muscarinic antagonists. Carbachol increased the formation of 3H-inositol phosphates (IPs) in a dose-dependent manner in both ileal smooth muscle and the frontal cortex of rats. The rank order of muscarinic antagonists for inhibition of IP formation induced by carbachol was 4-DAMP = atropine > pirenzepine > AF-DX 116 in guinea pig ileal smooth muscle. In ileal smooth muscle, the inhibition by the M1 antagonist pirenzepine was about 15 times less than that by atropine. However, in the rat frontal cortex, the inhibition by pirenzepine was only about 3 times less than that by atropine. The inhibitory effect of the M2 antagonist AF-DX 116 was weak in both ileal muscle and the frontal cortex. The M3 antagonist 4-DAMP strongly inhibited carbachol-induced IP formation in ileal smooth muscle. The rank order of muscarinic antagonists for inhibition of contraction induced by 10(-7) M carbachol was atropine > or = 4-DAMP > pirenzepine > AF-DX 116. These results suggest that both IP formation and the contractile response induced by muscarinic agonists are mediated through the muscarinic M3 subtype in guinea pig ileum.
我们利用毒蕈碱拮抗剂研究了介导豚鼠回肠纵行平滑肌中磷酸肌醇水解和收缩的毒蕈碱受体的药理学亚型。卡巴胆碱在大鼠回肠平滑肌和额叶皮质中均以剂量依赖性方式增加3H-肌醇磷酸（IPs）的生成。在豚鼠回肠平滑肌中，毒蕈碱拮抗剂抑制卡巴胆碱诱导的IP生成的效价顺序为4-二甲基氨基吡啶 = 阿托品 > 哌仑西平 > AF-DX 116。在回肠平滑肌中，M1拮抗剂哌仑西平的抑制作用比阿托品约小15倍。然而，在大鼠额叶皮质中，哌仑西平的抑制作用仅比阿托品约小3倍。M2拮抗剂AF-DX 116在回肠肌和额叶皮质中的抑制作用均较弱。M3拮抗剂4-二甲基氨基吡啶强烈抑制卡巴胆碱诱导的回肠平滑肌中IP的生成。毒蕈碱拮抗剂抑制10(-7) M卡巴胆碱诱导的收缩的效价顺序为阿托品 > 或 = 4-二甲基氨基吡啶 > 哌仑西平 > AF-DX 116。这些结果表明，在豚鼠回肠中，毒蕈碱激动剂诱导的IP生成和收缩反应均通过毒蕈碱M3亚型介导。
