THE DIHYDROPYRIDINE NITRENDIPINE INHIBITS [H-3] 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 [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.