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  • Title: Effects of verapamil on the release of different neurotransmitters.
    Author: Sitges M, Reyes A.
    Journal: J Neurosci Res; 1995 Apr 01; 40(5):613-21. PubMed ID: 7602614.
    Abstract:
    The effect of verapamil on resting and depolarization-induced monoamine release was investigated in rat hippocampal synaptosomes prelabeled with [3H]-5-hydroxytryptamine (HT) or [3H]-norepinephrine (NE) and rat striatal synaptosomes prelabeled with [3H]-dopamine (DA). Verapamil (50 microM) completely abolishes high K(+)-induced [3H]-NE release, but paradoxically facilitates high K(+)-induced [3H]-5-HT and [3H]-DA release. All these high K(+)-evoked responses were Ca2+ dependent. Verapamil does not modify [3H]-NE baseline release, but increases dose dependently [3H]-5-HT and [3H]-DA baseline release. Verapamil (10 microM, for 5 min) increases endogenous DA release (70%) and endogenous 5-HT release (40%) independently on the presence of external Ca2+. The total amount of these monoamines (released plus retained by the preparation) and their metabolites (DOPAC and 5-HIAA) was similar in control and verapamil-treated synaptosomes. Verapamil displaces [3H]-spiroperidol specific binding (Ki of 2.4 x 10(-6) M) and [3H]-SCH-23390 specific binding (Ki of 9 x 10(-6) M) from striatal synaptosomal membranes, and [3H]-5-HT specific binding (Ki of 3 x 10(-5) M) from hippocampal synaptosomal membranes. It is concluded that in addition to the Ca2+ antagonistic properties of verapamil on the Ca(2+)-dependent, depolarization-induced release of some neurotransmitters [gamma aminobutyric acid (GABA and NE)], another mechanism probably mediated by presynaptic receptors underlies the effects of verapamil on DA and 5-HT release from discrete brain regions.
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