MUSCARINIC RECEPTOR SUBTYPE MEDIATING VASODILATION IN FELINE MIDDLE CEREBRAL-ARTERY EXHIBITS M3 PHARMACOLOGY
MUSCARINIC RECEPTOR SUBTYPE MEDIATING VASODILATION IN FELINE MIDDLE CEREBRAL-ARTERY EXHIBITS M3 PHARMACOLOGY
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DOI：
10.1016/0014-2999(90)90476-m
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发表时间：
1990-03-20
影响因子：
5
通讯作者：
HAMEL, E
中科院分区：
文献类型：
--
作者：
DAUPHIN, F;HAMEL, E
通过记录猫离体大脑中动脉预收缩段平滑肌的等长张力，研究了毒蕈碱受体亚型介导内皮依赖性舒张的性质。由几种激动剂（乙酰胆碱（ACh）、乙酰-β-乙酰胆碱（ACh））诱导的舒张甲基胆碱、氧震颤素、卡巴胆碱和McN-A-343）。还估计了选择性（哌仑西平、双环胺、己二酚宁、AF-DX 116、甲氧六明、加拉明、4-二苯乙酰氧基-N-甲基哌啶碘甲烷（4-DAMP）和六氢硅-地芬尼多（HHSiD））和非选择性拮抗剂（阿托品、东莨菪碱和奎宁环二苯羟乙酸酯（QNB））阻断ACh诱导的松弛的能力。选择性差的M1激动剂McN-A-343的弱活性以及哌仑西平和阿地非宁的中等亲和力倾向于排除M1毒蕈碱受体作为胆碱能松弛的主要介质。AF-DX 116和甲氧四明的低亲和力进一步表明脑血管毒蕈碱受体不对应于M2心脏syb型。与此相反，4-DAMP和HHSiD有力地抑制乙酰胆碱诱导的松弛与亲和力类似的报告在M3腺体受体。我们的结论是，一个网站类似的药理学M3毒蕈碱受体亚型负责猫大脑中动脉的胆碱能松弛。
The nature of the muscarinic receptor subtype mediating the endothelium-dependent relaxation of the cat midd cerebral artery was investigated in vitro by recording the smooth muscle isometric tension of precontracted arteri segments. Relaxation induced by several agonists (acetylcholine (ACh), acetyl-.beta.-methylcholine, oxotremorine, carbachol and McN-A-343) was recorded. The ability of selective (pirenzepine, dicyclomine, adiphenine, AF-DX 116, methoctramine, gallamine, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) and hexahydro-sila-difenidol (HHSiD)) and non-selective antagonists (atropine, scopolamine and quinuclidinyl benzilate (QNB)) to block the relaxation induced by ACh was also estimated. The weak activity of the poorly selective M1 agonist McN-A-343 together with the intermediate affinity of pirenzepine and adiphenine tend to exclude the M1 muscarinic receptor as the primary mediator of the cholinergic relaxation. The low affinity of AF-DX 116 and methoctramine further suggested that the cerebrovascular muscarinic receptor does not correspond to the M2 cardiac sybtype. In contrast, 4-DAMP and HHSiD potently inhibited the ACh-induced relaxation with affinities similar to those reported at the M3 glandular receptor. We conclude that a site similar to the pharmacological M3 muscarinic receptor subtype is responsible for the cholinergic relaxation of the cat middle cerebral artery.