（RS）-α-环丙基-4-膦酰基苯甘氨酸（（RS）-CPPG）的作用，一种强效且选择性的代谢型谷氨酸受体拮抗剂。

The effects of (RS)-alpha-cyclopropyl-4-phosphonophenylglycine ((RS)-CPPG), a potent and selective metabotropic glutamate receptor antagonist.

Toms N J, Jane D E, Kemp M C, Bedingfield J S, Roberts P J

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

Br J Pharmacol. 1996 Nov;119(5):851-4. doi: 10.1111/j.1476-5381.1996.tb15750.x.

Abstract

In this study we describe the potent antagonist activity of a novel metabotropic glutamate (mGlu) receptor antagonist (RS)-alpha-cyclopropyl-4-phosphonophenylglycine ((RS)-CPPG) which exhibits selectivity for mGlu receptors (group II and III) negatively coupled to adenylyl cyclase in the adult rat cortex. 2. Both the L-2-amino-4-phosphonobutyrate (L-AP4) and (2S, 1'S, 2'S)-2-(carboxycyclopropyl)glycine (L-CCG-1) inhibition of forskolin-stimulated cyclic AMP accumulation were potently reversed by (RS)-CPPG (IC50 values: 2.2 +/- 0.6 nM and 46.2 +/- 18.2 nM, respectively). 3. In contrast, (RS)-CPPG acted as a weak antagonist against group I mGlu receptors. In neonatal rat cortical slices, (RS)-CPPG antagonized (KB = 0.65 +/- 0.07 mM) (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD)-stimulated phosphoinositide hydrolysis. (RS)-CPPG (100 microM) failed to influence L-quisqualate-stimulated phosphoinositide hydrolysis in cultured cerebellar granule cells. 4. In the rat cerebral cortex, (RS)-CPPG is the most potent antagonist of group II/III mGlu receptors yet described (with 20 fold selectivity for group III mGlu receptors), having negligible activity at group I mGlu receptors.

摘要

在本研究中，我们描述了一种新型代谢型谷氨酸（mGlu）受体拮抗剂（RS）-α-环丙基-4-膦酰基苯甘氨酸（（RS）-CPPG）的强效拮抗活性，该拮抗剂对成年大鼠皮质中与腺苷酸环化酶负偶联的mGlu受体（II组和III组）具有选择性。2. （RS）-CPPG能有效逆转L-2-氨基-4-膦酰基丁酸（L-AP4）和（2S，1'S，2'S）-2-（羧基环丙基）甘氨酸（L-CCG-1）对福司可林刺激的环磷酸腺苷积累的抑制作用（IC50值分别为2.2±0.6 nM和46.2±18.2 nM）。3. 相比之下，（RS）-CPPG对I组mGlu受体的拮抗作用较弱。在新生大鼠皮质切片中，（RS）-CPPG拮抗（KB = 0.65±0.07 mM）（1S，3R）-1-氨基环戊烷-1，3-二羧酸（（1S，3R）-ACPD）刺激的磷酸肌醇水解。（RS）-CPPG（100μM）未能影响培养的小脑颗粒细胞中L-喹啉酸刺激的磷酸肌醇水解。4. 在大鼠大脑皮质中，（RS）-CPPG是迄今所描述的II/III组mGlu受体最有效的拮抗剂（对III组mGlu受体具有20倍的选择性），对I组mGlu受体的活性可忽略不计。