THE DIHYDROPYRIDINE NITRENDIPINE INHIBITS [H-3] MK-801 BINDING TO MOUSE-BRAIN SECTIONS

被引:14
作者
FILLOUX, FM
FITTS, RC
SKEEN, GA
WHITE, HS
机构
[1] UNIV UTAH,SCH MED,DEPT NEUROL,SALT LAKE CITY,UT 84132
[2] UNIV UTAH,SCH MED,DEPT PEDIAT,SALT LAKE CITY,UT 84132
[3] UNIV UTAH,SCH MED,DEPT PSYCHIAT,SALT LAKE CITY,UT 84132
[4] UNIV UTAH,SCH MED,DEPT PHARMACOL,SALT LAKE CITY,UT 84132
[5] DEPT TOXICOL,SALT LAKE CITY,UT 84132
[6] ANTICONVULSANT DRUG DEV PROGRAM,SALT LAKE CITY,UT 84132
来源
EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION | 1994年 / 269卷 / 03期
关键词
CA2+; CHANNEL; L-TYPE; DIHYDROPYRIDINE; NITRENDIPINE; MK; 801; VOLTAGE-SENSITIVE; NMDA RECEPTOR; DIBENZOCYCLOHEPTENEIMINE;
D O I
10.1016/0922-4106(94)90040-X
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The L-type Ca2+ channel antagonist nitrendipine inhibits N-methyl-D-aspartate (NMDA)-activated Ca2+ flux into cerebellar granule cells, and [H-3] dibenzocyclohepteneimine ([H-3]MK 801) binding to mouse cerebral cortical and hippocampal membranes. To further study this interaction between nitrendipine and NMDA-activated channels, the effects of several L-channel active agents on [H-3]MK 801 binding to mouse brain were investigated in an autoradiographic assay. Serial slide-mounted sagittal sections of mouse brain were labeled with [H-3]MK 801 in the presence of varying concentrations of the L-channel active agents nitrendipine, nimodipine, nifedipine, Bay K 8644, and verapamil. Nitrendipine potently displaced 2 nM [H-3]MK 801 binding to mouse brain sections (IC50 = 89.8 nM). Dose-dependent inhibition of [H-3]MK 801 binding by nitrendipine was demonstrated in most brain regions examined. 10(-5) M and 10(-8) M concentrations of the other dihydropyridines studied, and of verapamil, were without effect. The data supports a unique, direct interaction between nitrendipine and the NMDA-activated ion channel.
引用
收藏
页码:325 / 330
页数:6
相关论文
共 30 条
[1]  
ABELE AE, 1990, NEURON, V2, P413
[2]   PHARMACOLOGICAL EVIDENCE THAT THE NON-NEURONAL DIAZEPAM BINDING-SITE IN PRIMARY CULTURES OF GLIAL-CELLS IS ASSOCIATED WITH A CALCIUM-CHANNEL [J].
BENDER, AS ;
HERTZ, L .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1985, 110 (02) :287-288
[3]   QUANTITATIVE AUTORADIOGRAPHY OF [H-3]-MK-801 BINDING-SITES IN MAMMALIAN BRAIN [J].
BOWERY, NG ;
WONG, EHF ;
HUDSON, AL .
BRITISH JOURNAL OF PHARMACOLOGY, 1988, 93 (04) :944-954
[5]   1,4-DIHYDROPYRIDINES AS ANTAGONISTS OF PLATELET-ACTIVATING-FACTOR .1. SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF 2-(4-HETEROCYCLYL)PHENYL DERIVATIVES [J].
COOPER, K ;
FRAY, MJ ;
PARRY, MJ ;
RICHARDSON, K ;
STEELE, J .
JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (17) :3115-3129
[6]   ANTICONVULSANT PROFILE OF THE DIHYDROPYRIDINE CALCIUM-CHANNEL ANTAGONISTS, NITRENDIPINE AND NIMODIPINE [J].
DOLIN, SJ ;
HUNTER, AB ;
HALSEY, MJ ;
LITTLE, HJ .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1988, 152 (1-2) :19-27
[7]   IDENTIFICATION OF A NOVEL NMDA RECEPTOR IN RAT CEREBELLUM [J].
EBERT, B ;
WONG, EHF ;
KROGSGAARDLARSEN, P .
EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION, 1991, 208 (01) :49-52
[8]  
HALEEN SJ, 1989, J PHARMACOL EXP THER, V250, P22
[9]   THE MECHANISM OF ACTION AND PHARMACOLOGICAL SPECIFICITY OF THE ANTICONVULSANT NMDA ANTAGONIST MK-801 - A VOLTAGE CLAMP STUDY ON NEURONAL CELLS IN CULTURE [J].
HALLIWELL, RF ;
PETERS, JA ;
LAMBERT, JJ .
BRITISH JOURNAL OF PHARMACOLOGY, 1989, 96 (02) :480-494
[10]   COMBINED TREATMENT WITH MK-801 AND NICARDIPINE REDUCES GLOBAL ISCHEMIC DAMAGE IN THE GERBIL [J].
HEWITT, K ;
CORBETT, D .
STROKE, 1992, 23 (01) :82-86