EFFECTS OF VERAPAMIL ON THE RELEASE OF DIFFERENT NEUROTRANSMITTERS

The effect of verapamil on resting and depolarization-induced monoamine release was investigated in rat hippocampal synaptosomes prelabeled with [H-3]-5-hydroxytryptamine (HT) or [H-3]-norepinephrine (NE) and rat striatal synaptosomes prelabeled with [H-3]-dopamine (DA), Verapamil (50 mu M) completely abolishes high K+-induced [H-3]-NE release, but paradoxically facilitates high K+-induced [H-3]-5-HT and [H-3]-DA release, All these high K+-evoked responses were Ca2+ dependent. Verapamil does not modify [H-3]-NE baseline release, but increases dose dependently [H-3]-5-HT and [H-3]-DA baseline release. Verapamil (10 mu M, 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 [H-3]-spiroperidol specific binding (K-i of 2.4 x 10(-6) M) and [H-3]-SCH-23390 specific binding (K-i of 9 x 10(-6) M) from striatal synaptosomal membranes, and [H-3]-5-HT specific binding (K-i 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 Ca2+-dependent, depolarization-induced release of some neurotransmitters [gamma aminobutyric acid (GABA and NE)I, another mechanism probably mediated by presynaptic receptors underlies the effects of verapamil on DA and 5-HT release from discrete brain regions. (c) 1995 Wiley-Liss, Inc.