Effects of verapamil on the release of different neurotransmitters

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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 μM) 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 μM, 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 × 10−6M) and [3H]‐SCH‐23390 specific binding (Ki of 9 × 10−6M) from striatal synaptosomal membranes, and [3H]‐5‐HT specific binding (Ki of 3 × 10−5M) from hippocampal synaptosomal membranes. It is concluded that in addition to the Ca2+ antagonistic properties of verapamil on the Ca2+‐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.