成年大鼠皮质切片中环磷酸腺苷偶联的代谢型谷氨酸受体激动剂

Agonists of cyclic AMP-coupled metabotropic glutamate receptors in adult rat cortical slices.

作者信息

Kemp M C, Jane D E, Tse H W, Roberts P J

机构信息

Department of Pharmacology, School of Medical Sciences, University of Bristol, UK.

出版信息

Eur J Pharmacol. 1996 Aug 1;309(1):79-85. doi: 10.1016/0014-2999(96)00314-7.

DOI:10.1016/0014-2999(96)00314-7

PMID:8864697

Abstract

A number of potential Group 2 and Group 3 metabotropic glutamate receptor (mGlu receptor) agonists were investigated in adult rat brain cerebrocortical slices. The rank order of their potency in inhibiting forskolin-stimulated adenylyl cyclase was found to be: (S)-2-amino-2-methyl-4-phosphonobutyric acid (MAP4) > (2S,1'S,2'S)-2-(2-carboxycyclopropyl)glycine (L-CCG-I) > (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3S-ACPD) > (1S,3R)-1-aminocyclopentane-1, 3-dicarboxylic acid (1S,3R)-ACPD) > (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) > (S) -2-methylglutamate ((S)-MG) > L-glutamate > (2S,1'S, 2'S)-2-(2-carboxycyclopropyl)alanine (MCCG) > L-2-amino-4-phosphonobutyric acid (L-AP4) > L-serine-O-phosphate (SOP). The finding that (S)-2-amino-2-methyl-4-phosphonobutyric acid was the most potent agonist at these metabotropic glutamate receptors is in contrast to its observed potent mGlu receptor antagonist action in the neonatal rat spinal cord.

摘要

在成年大鼠脑皮质切片中研究了多种潜在的第2组和第3组代谢型谷氨酸受体（mGlu受体）激动剂。发现它们抑制福斯高林刺激的腺苷酸环化酶的效力顺序为：(S)-2-氨基-2-甲基-4-膦酰丁酸（MAP4）>(2S,1'S,2'S)-2-(2-羧基环丙基)甘氨酸（L-CCG-I）>(1S,3S)-1-氨基环戊烷-1,3-二羧酸（1S,3S-ACPD）>(1S,3R)-1-氨基环戊烷-1,3-二羧酸（1S,3R)-ACPD）>(2S,1'R,2'R,3'R)-2-(2,3-二羧基环丙基)甘氨酸（DCG-IV）>(S)-2-甲基谷氨酸（(S)-MG）>L-谷氨酸>(2S,1'S,2'S)-2-(2-羧基环丙基)丙氨酸（MCCG）>L-2-氨基-4-膦酰丁酸（L-AP4）>L-丝氨酸-O-磷酸（SOP）。(S)-2-氨基-2-甲基-4-膦酰丁酸在这些代谢型谷氨酸受体上是最有效的激动剂，这一发现与其在新生大鼠脊髓中观察到的强效mGlu受体拮抗剂作用形成对比。