NDLI: Characterization of dihydropyridine-sensitive calcium channels in rat brain synaptosomes.

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Characterization of dihydropyridine-sensitive calcium channels in rat brain synaptosomes.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Woodward, J. J. Cook, M. E. Leslie, S. W.
Description	Author Affiliation: Woodward JJ ( Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas, Austin 78712.);
Abstract	We examined the effects of dihydropyridine Ca2+-channel agonists on synaptosomal voltage-dependent Ca2+ entry and endogenous dopamine release. The (-) isomer of Bay K 8644 and the (+) isomer of Sandoz compound 202-791 were 100-1000 times more potent than their respective opposite enantiomers in enhancing Ca2+ uptake and dopamine release from striatal synaptosomes. The active isomer of each of these compounds increased Ca2+ entry and dopamine release to the same extent at a concentration of 1 nM. Fast-phase Ca2+ entry into synaptosomes isolated from cerebellum, cortex, and hippocampus was sensitive to nanomolar concentrations of Bay K 8644. No effect of Bay K 8644 was observed in synaptosomes isolated from brainstem. Bay K 8644 increased synaptosomal Ca2+ uptake and endogenous dopamine release from striatal synaptosomes only during the initial seconds of KCl-induced depolarization. The greatest increase was observed during the first second of depolarization. No effect was observed after greater than or equal to 5 sec of depolarization. Bay K 8644 did not alter Ca2+ uptake or dopamine release under resting conditions (5 mM KCl) or in response to KCl at greater than 15 mM. The activity of Bay K 8644 was also attenuated by lowering the concentrations of divalent cations in the incubation medium. Agonist activity was observed at Mg2+ concentrations greater than 500 microM (Ca2+ held at 100 microM) and Ca2+ concentrations greater than 100 microM (Mg2+ held at 1000 microM). These results suggest that the Ca2+ channels present in synaptosomes are sensitive to nanomolar concentrations of dihydropyridine agonists under a narrow range of experimental conditions.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	19
Volume Number	85
Language	English
Publisher	National Academy of Sciences
Publisher Date	1988-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Brain Cytology Calcium Pharmacokinetics Dihydropyridines Pharmacology Ion Channels Drug Effects Synaptosomes Animals Metabolism Centrifugation, Density Gradient Dopamine Potassium Chloride Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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