SUBTYPES OF METABOTROPIC EXCITATORY AMINO-ACID RECEPTOR DISTINGUISHED BY STEREOISOMERS OF THE RIGID GLUTAMATE ANALOG, 1-AMINOCYCLOPENTANE-1,3-DICARBOXYLATE

被引:27
作者
CARTMELL, J
CURTIS, AR
KEMP, JA
KENDALL, DA
ALEXANDER, SPH
机构
[1] UNIV NOTTINGHAM HOSP,QUEENS MED CTR,SCH MED,DEPT PHYSIOL & PHARMACOL,NOTTINGHAM NG7 2UH,ENGLAND
[2] MERCK SHARP & DOHME LTD,NEUROSCI RES CTR,HARLOW,ENGLAND
基金
英国惠康基金;
关键词
EXCITATORY AMINO ACID; 1-AMINOCYCLOPENTANE-1,3-DICARBOXYLATE; PHOSPHOINOSITIDE TURNOVER; CYCLIC AMP; ADENOSINE-A(2B) RECEPTOR;
D O I
10.1016/0304-3940(93)90088-3
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The 1R,3R- and 1R,3S-isomers of 1-aminocyclopentane-1,3-dicarboxylate (ACPD) failed to stimulate phosphoinositide turnover or modify A2b adenosine receptor-stimulated cyclic AMP accumulation in guinea-pig cerebral cortical slices. In contrast, both 1S,3R- and 1S,3S-ACPD elicited concentration-dependent stimulations of phosphoinositide turnover (EC50 values 35 and 97 muM, respectively) and potentiated A2b-stimulated cAMP formation (17 and 58 muM, respectively). When forskolin was used to elevate cyclic AMP levels, however, all four isomers elicited concentration-dependent inhibitions of cyclic AMP formation to the same extent (approximately 90% inhibition). For this response the rank order of potencies were (IC50 values): 1S,3S-(0.9 muM) > 1S,3R-(2.1 muM) > 1R,3R-(237 muM) > 1R,3S-ACPD (approximately 1 mM). These data suggest the presence in guinea-pig cerebral cortex of two distinct subtypes of ACPD receptor coupled to phosphoinositide hydrolysis (and the potentiation of A2b receptor-stimulated cAMP formation) and the inhibition of forskolin-stimulated cAMP accumulation. Furthermore, our results indicate the usefulness of 1S,3S-ACPD as a tool to selectively activate one of these subtypes.
引用
收藏
页码:107 / 110
页数:4
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