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Interactions of local anesthetics with neuronal 1,4-dihydropyridine binding sites
1Department of Biochemical Pharmacology, School of Pharmacy, State University of New York at Buffalo 14260.
Abstract:
A series of local anesthetics competed with 1,4-dihydropyridine [3H]PN 200,110 binding to synaptosomes from guinea pig cerebral cortex synaptosomes. Dibucaine (10(-3)M) increased the dissociation rate of bound [3H]PN 200,110 consistent with an indirect, rather than competitive, interaction between local anesthetics and the 1,4-dihydropyridine site. The binding activities were compared to those previously available for local anesthetic competition with [3H]batrachotoxinin benzoate binding at a Na+ channel site. A linear correlation was observed between the two sets of activities with significantly higher activities being exhibited at the Na+ channel site. This relationship is consistent with the significant structural homologies exhibited between Na+ and Ca2+ channels.