大鼠培养小脑颗粒细胞中代谢型谷氨酸受体刺激的磷酸肌醇水解的特性研究
Characterization of metabotropic glutamate receptor-stimulated phosphoinositide hydrolysis in rat cultured cerebellar granule cells.
作者信息
Toms N J, Jane D E, Tse H W, Roberts P J
机构信息
Department of Pharmacology, School of Medical Sciences, University of Bristol.
出版信息
Br J Pharmacol. 1995 Dec;116(7):2824-7. doi: 10.1111/j.1476-5381.1995.tb15932.x.
Abstract
- The pharmacology of excitatory amino acid (EAA)-stimulated phosphoinositide (PI) hydrolysis, monitored via [3H]-inositol monophosphate accumulation, was investigated in primary cultures of rat cerebellar granule cells. 2. EAA-stimulated PI hydrolysis peaked after 4-5 days in vitro and subsequently declined. 3. The agonist order of potency was found to be (EC50): L-quisqualic acid (Quis) (2 microM) >> L-glutamate (50 microM) > (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD) (102 microM). L-Glutamate (Emax = 873% of basal activity) elicited the largest stimulation of PI hydrolysis, whereas Quis (Emax = 603%) and (1S,3R)-ACPD (Emax = 306%) produced somewhat lower stimulations. 4. Several phenylglycine derivatives were found to be active in inhibiting 2 microM Quis-stimulated PI hydrolysis, in order of potency (IC50): (S)-4-carboxy-3-hydroxyphenylglycine (41 microM) > or = (S)-4-carboxyphenylglycine (51 microM) >> (+)-alpha-methyl-4-carboxyphenylglycine (243 microM). 5. Cultured cerebellar granule cells of the rat appear to have Group I mGluR pharmacology similar to that reported for cloned mGluR1 and provide an ideal system for investigating novel mGluR1 ligands in a native environment.
摘要
- 通过[3H]-肌醇单磷酸积累监测兴奋性氨基酸（EAA）刺激的磷酸肌醇（PI）水解的药理学，在大鼠小脑颗粒细胞原代培养物中进行了研究。2. EAA刺激的PI水解在体外4-5天后达到峰值，随后下降。3. 发现激动剂效力顺序为（EC50）：L-喹啉酸（Quis）（2 microM）>> L-谷氨酸（50 microM）>（1S，3R）-1-氨基环戊烷-1,3-二羧酸（（1S，3R）-ACPD）（102 microM）。L-谷氨酸（Emax =基础活性的873%）引起PI水解的最大刺激，而Quis（Emax = 603%）和（1S，3R）-ACPD（Emax = 306%）产生的刺激略低。4. 发现几种苯甘氨酸衍生物在抑制2 microM Quis刺激的PI水解方面具有活性，效力顺序为（IC50）：（S）-4-羧基-3-羟基苯甘氨酸（41 microM）≥（S）-4-羧基苯甘氨酸（51 microM）>>（+）-α-甲基-4-羧基苯甘氨酸（243 microM）。5. 大鼠培养的小脑颗粒细胞似乎具有与报道的克隆mGluR1相似的I组代谢型谷氨酸受体药理学，为在天然环境中研究新型mGluR1配体提供了理想的系统。
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