Biochemical and behavioral evidence for muscarinic autoreceptors in the CNS.
Biochemical and behavioral evidence for muscarinic autoreceptors in the CNS.
复制标题
中枢神经系统中毒蕈碱自身受体的生化和行为证据。
DOI：
10.1016/0006-8993(90)91026-d
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发表时间：
1990
期刊：
影响因子：
2.9
通讯作者：
Mazloum,Z
中科院分区：
文献类型：
--
作者：
Hoss,W;MesserJr,WS;MonsmaJr,FJ;Miller,MD;Ellerbrock,BR;Scranton,T;Ghodsi-Hovsepian,S;Price,MA;Balan,S;Mazloum,Z
Muscarinic autoreceptors of the M2subclass were examined in rat forebrain using a number of different methodologies, including receptor autoradiography and image analysis, regulation of acetylcholine release, phosphoinositide turnover, low-KmGTP hydrolysis, and behavioral analysis. The relatively minor population of M2receptors in coronal sections was visualized by autoradiography and image analysis using [3H]quinuclidinyl benzilate in the presence of a concentration of pirenzepine that blocked most of M1(and M4) receptors. The highest densities of M2receptors in forebrain regions were found in the outer layers of the cortex, CA1 region of the hippocampus and striatum. The M2-, but not M1-selective antagonists were able to block the oxotremorine-induced attenuation of acetylcholine release in forebrain synaptosomes. Low concentrations of the M2-selective antagonist gallamine increased phosphoinositide turnover, which is thought to be an M1postsynaptic response in the forebrain, in brain slices by a Ca2+-dependent mechanism. The M2-selective agonist oxotremorine produced a substantial stimulation of low-KmGTPase in cortical membranes, suggesting that M2forebrain receptors are efficiently coupled to G-proteins in the cortex. Behavioral signs of cholinergic stimulation were observed after intracerebroventricular injections of M2-, but not M1-selective antagonists. It is suggested that a minor population of foregrain M2receptors regulates acetylcholine release by a mechanism that includes coupling through G-proteins presynaptically at synapses for which the postsynaptic response involves phosphoinositide turnover. Selective blockade of these receptors produces both biochemical and behavioral signs of acetylcholine release.
