PHARMACOLOGICAL CHARACTERIZATION OF THE N-METHYL-D-ASPARTATE (NMDA) RECEPTOR RECOGNITION SITE IN PORCINE CEREBRAL CORTICAL MEMBRANES USING [H-3] CGP-39653

被引:5
作者
BANKS, MDG [1 ]
SANDBERG, MP [1 ]
FOWLER, CJ [1 ]
机构
[1] ASTRA PAIN CONTROL AB,PRECLIN RES & DEV,NOVUM UNIT,S-14157 HUDDINGE,SWEDEN
来源
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-PHYSIOLOGY | 1995年 / 111卷 / 01期
关键词
PORCINE CEREBRAL CORTEX; EXCITATORY AMINO ACID; NMDA (N-METHYL-D-ASPARTATE); RECEPTOR BINDING; SATURATION ANALYSIS; COMPETITION ANALYSIS; H-3] CGP 39653; TRITON X-100; PH DEPENDENCY;
D O I
10.1016/0300-9629(95)98517-K
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The high-affinity NMDA receptor competitive antagonist [H-3]-CGP 39653 binds to Triton X-100 (0.04%) treated porcine cerebral cortex membranes in a saturable and reversible manner, with a K-D of 6.1 +/- 0.97 nM and a B-max of 944 +/- 55 fmol/mg protein. Association of ligand with the recognition site was rapid (estimated k(1) = 1.1 x 10(7) M(-1) min(-1)), and a steady state was reached within 30 min of incubation at 4 degrees C. Dissociation was also rapid (estimated k(-1) = 0.2 min(-1)). The pharmacology of the binding site was similar to that for the rat brain, with mean pIC(50) values (Hill slopes in parentheses, ''indicating significant difference from unity) of 7.54 (0.51*), 6.99 (0.68*), 6.98 (0.71), 6.63 (0.80*), 6.31 (0.62*) and 5.17 (0.78) for R-CPP, L-glutamate, CGS 19755, cis-2,4-methanoglutamate, L-aspartate and NMDA, respectively. Other compounds (glycine, MK-801, kainate, S-AMPA and magnesium ions), previously observed not to interact competitively with the NMDA binding recognition site, showed a low affinity for the porcine cerebral cortex [H-3]-CGP 39653 binding site. It is concluded that the pharmacological properties of the NMDA receptor recognition site labelled by [H-3]-CGP 39653 are similar in the pig and rat cerebral cortices.
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页码:39 / 46
页数:8
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