BAY K 8644, a 1,4-Dihydropyridine Ca2+ Channel Activator: Dissociation of Binding and Functional Effects in Brain Synaptosomes |
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Authors: | D. Rampe R. A. Janis D. J. Triggle |
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Affiliation: | Department of Biochemical Pharmacology, School of Pharmacy, State University of New York at Buffalo, Buffalo, New York;Miles Institute for Preclinical Pharmacology, New Haven, Connecticut, U.S.A. |
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Abstract: | K+-stimulated 45Ca2+ uptake into rat brain and guinea pig cerebral cortex synaptosomes was measured at 10 s and 90 s at K+ concentrations of 5-75 mM. Net increases in 45Ca2+ uptake were observed in rat and guinea pig brain synaptosomes. 45Ca2+ uptake under resting or depolarizing conditions was not increased by the 1,4-dihydropyridine BAY K 8644, which has been shown to activate Ca2+ channels in smooth and cardiac muscle. High-affinity [3H]nitrendipine binding in guinea pig synaptosomes (KD = 1.2 X 10(-10) M, Bmax = 0.56 pmol mg-1 protein) was competitively displaced with high affinity (IC50 2.3 X 10(-9) M) by BAY K 8644. Thus high-affinity Ca2+ channel antagonist and activator binding sites exist in synaptosome preparations, but their relationship to functional Ca2+ channels is not clear. |
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Keywords: | Calcium antagonists Calcium uptake Nitrendipine BAY K 8644 Synaptosomes |
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