The dihydropyridine nitrendipine inhibits [3H]MK 801 binding to mouse brain sections.
The L-type Ca2+ channel antagonist nitrendipine inhibits N-methyl-D-aspartate (NMDA)-activated Ca2+ flux into cerebellar granule cells, and [3H]dibenzocyclohepteneimine ([3H]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 [3H]MK 801 binding to mouse brain were investigated in an autoradiographic assay. Serial slide-mounted sagittal sections of mouse brain were labeled with [3H]MK 801 in the presence of varying concentrations of the L-channel active agents nitrendipine, nimodipine, nifedipine, Bay K 8644, and verapami. Nitrendipine potently displaced 2 nM [3H]MK 801 binding to mouse brain sections (IC50 = 89.8 nM). Dose-dependent inhibition of [3H]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.
Filloux
F M
FM
Department of Neurology, University of Utah School of Medicine, Salt Lake City 84132.
Fitts
R C
RC
Skeen
G A
GA
White
H S
HS
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology*; D012984:Software; D014700:Verapamil / Q000494:pharmacology
D009553:Nimodipine; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine; D014700:Verapamil; D009543:Nifedipine; D002118:Calcium