title: The dihydropyridine nitrendipine inhibits [3H]MK 801 binding to mouse brain sections.
abstract: 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.
authors.affiliation: Department of Neurology, University of Utah School of Medicine, Salt Lake City 84132.
authors.forename: F M
authors.initials: FM
authors.lastname: Filloux
authors.forename: R C
authors.initials: RC
authors.lastname: Fitts
authors.forename: G A
authors.initials: GA
authors.lastname: Skeen
authors.forename: H S
authors.initials: HS
authors.lastname: White
mesh_terms: 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
chemical_list: 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