3,5-二羟基苯甘氨酸是大鼠海马体中磷酸肌醇连接的代谢型谷氨酸受体的高度选择性激动剂。

3,5-dihydroxyphenylglycine is a highly selective agonist for phosphoinositide-linked metabotropic glutamate receptors in the rat hippocampus.

作者信息

Schoepp D D, Goldsworthy J, Johnson B G, Salhoff C R, Baker S R

机构信息

Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285.

出版信息

J Neurochem. 1994 Aug;63(2):769-72. doi: 10.1046/j.1471-4159.1994.63020769.x.

DOI:10.1046/j.1471-4159.1994.63020769.x

Abstract

Metabotropic glutamate receptors (mGluRs) are a heterogeneous family of G protein-coupled glutamate receptors that are linked to multiple second messenger systems in the CNS. In this study the selectivity of mGluR agonists for different mGluR second messenger effects was characterized in slices of the rat hippocampus. The mGluR agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid and (2S,3S,4S)alpha-(carboxycyclopropyl)glycine produced multiple effects on second messengers that included enhanced phosphoinositide hydrolysis in both adult and neonatal rat hippocampus, inhibition of forskolin-stimulated cyclic AMP (cAMP) formation in adult tissue, and increases in basal cAMP formation in the neonatal hippocampus. In contrast, 3,5-dihydroxyphenylglycine was potent and effective in increasing phosphoinositide hydrolysis in both adult and neonatal hippocampus but unlike the other mGluR agonists did not inhibit forskolin-stimulated cAMP formation (in the adult) or substantially enhance basal cAMP formation (in the neonate). Thus, in the rat hippocampus mGluR agonist-mediated increases or decreases in cAMP formation are not secondary to mGluR-mediated changes in phosphoinositide hydrolysis. Furthermore, 3,5-dihydroxyphenylglycine can be used to activate subpopulations of mGluRs coupled to phosphoinositide hydrolysis with minimal effects on cAMP-mGluR second messenger systems.

摘要

代谢型谷氨酸受体（mGluRs）是一类异质性的G蛋白偶联型谷氨酸受体家族，它们与中枢神经系统中的多种第二信使系统相关联。在本研究中，在大鼠海马切片中对mGluR激动剂对不同mGluR第二信使效应的选择性进行了表征。mGluR激动剂（1S，3R）-1-氨基环戊烷-1,3-二羧酸和（2S，3S，4S）α-（羧基环丙基）甘氨酸对第二信使产生多种效应，包括在成年和新生大鼠海马中增强磷酸肌醇水解、在成年组织中抑制福斯高林刺激的环磷酸腺苷（cAMP）形成以及在新生海马中增加基础cAMP形成。相比之下，3,5-二羟基苯甘氨酸在成年和新生海马中均能有效增强磷酸肌醇水解，但与其他mGluR激动剂不同的是，它不抑制福斯高林刺激的cAMP形成（在成年动物中）或显著增强基础cAMP形成（在新生动物中）。因此，在大鼠海马中，mGluR激动剂介导的cAMP形成增加或减少并非继发于mGluR介导的磷酸肌醇水解变化。此外，3,5-二羟基苯甘氨酸可用于激活与磷酸肌醇水解偶联的mGluR亚群，而对cAMP-mGluR第二信使系统的影响最小。