Biochemical and behavioral responses of pilocarpine at muscarinic receptor subtypes in the CNS. Comparison with receptor binding and low-energy conformations.
Biochemical and behavioral responses of pilocarpine at muscarinic receptor subtypes in the CNS. Comparison with receptor binding and low-energy conformations.
复制标题
毛果芸香碱对中枢神经系统毒蕈碱受体亚型的生化和行为反应。
DOI：
10.1016/0006-8993(90)91344-g
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发表时间：
1990
期刊：
影响因子：
2.9
通讯作者：
MesserJr,WS
中科院分区：
文献类型：
--
作者：
Hoss,W;Woodruff,JM;Ellerbrock,BR;Periyasamy,S;Ghodsi-Hovsepian,S;Stibbe,J;Bohnett,M;MesserJr,WS
匹罗卡品在体外进行了生化测试，以观察其刺激海马区肌醇磷脂(PI)周转的能力(M1/M3反应)，其中它显示35%的最大卡巴胆碱反应，EC50值为18μM；在大脑皮层(M2反应)，它显示低KmGTP酶，其中它具有最大卡巴胆碱反应的50%，EC50值为4.5μM。行为上，匹罗卡品能够修复由海马内注射AF64A产生的代表性记忆任务(对M1拮抗剂敏感)中的缺陷。用McroModel程序计算了23个质子化匹罗卡品的低能构象。结果表明，匹罗卡品是中枢M_1和M_2受体的部分激动剂。在行为方面，在记忆任务中，毛果芸香碱的M1效应明显占优势。也可以想象，不同构象的匹罗卡品在不同的M受体亚型上具有激动剂的活性。
Pilocarpine was tested biochemically in vitro for its ability to stimulate phosphoinositide (PI) turnover in the hippocampus (M1/M3responses) where it displayed 35% of the maximal carbachol response with an EC50value of 18 μM, andlow-KmGTPase in the cortex (M2response), where it had 50% of the maximal carbachol response with an EC50value of 4.5 μM. Behaviorally, pilocarpine was able to restore deficits in a representational memory task (sensitive to M1antagonists) produced by intrahippocampal injections of AF64A. Twenty-three low-energy conformations of protonated pilocarpine were generated using the program McroModel. The data indicate that pilocarpine is a partial agonist at both M1and M2muscarinic receptors in the CNS. Behaviorally, with respect to the memory task, M1effects of pilocarpine apparently predominate. It also is conceivable that different conformations of pilocarpine are active as agonist at different muscarinic receptor subtypes.