IN-VITRO BINDING OF[H-3]NIMODIPINE AND [H-3] CGS-19755 TO RAT-BRAIN IN FOCAL CEREBRAL-ISCHEMIA

Focal cerebral ischemia results in increased in vivo binding of calciu m channel antagonists to both the L-type voltage sensitive calcium cha nnel (VSCC) and the N-methyl-D-aspartate (NMDA) receptor-linked calciu m channel. It was the aim of this study to investigate the effect of f ocal cerebral ischemia on the in vitro binding of calcium channel anta gonists to rat brain. Quantitative autoradiography was used to measure regional in vitro binding of the L-type VSCC antagonist [H-3]nimodipi ne and the competitive NMDA receptor antagonist [H-3]CGS-19755 to rat brain following 4 h of irreversible focal cerebral ischemia. [H-3]Nimo dipine binding to the nonischemic hemisphere was characterized by one binding site with regional binding affinity (K-D) estimates ranging fr om 221 to 482 pM and maximal binding site densities (B-MAX) ranging fr om 13.2 (9.6-17.5) pmol/g tissue (estimate and 95% confidence interval ) in CA1 to 32.5 (26.5-39.9) pmol/g tissue in dentate. [H-3]CGS-19755 binding to the nonischemic hemisphere was characterized by K-D estimat es ranging from 59 to 97 nM and B-MAX values ranging from 143 (108-192 ) pmol/g tissue in cortex to 569 (515-641) pmol/g tissue in CA1. For [ H-3]CGS-19755 a model of two binding sites was applicable in several b rain regions. No difference in binding site densities or binding affin ities between ischemic and paired nonischemic structures (cortex and s triatum) was observed with either ligand. In vitro binding of [H-3]nim odipine and [H-3]CGS-19755 to ischemic brain failed to identify ischem ic-induced changes in calcium channel function previously reported by in vivo binding methods. (C) 1995 Academic Press, Inc.