Effects of verapamil on the release of different neurotransmitters

✍ Scribed by Dr. María Sitges; A. Reyes

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 962 KB
• Volume: 40
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.490400506

✦ Synopsis

The effect of verapamil on resting and depolarizationinduced monoamine release was investigated in rat hippocampal synaptosomes prelabeled with [3H]-5hydroxytryptamine (HT) or [3H]-norepinephrine (NE) and rat striatal synaptosomes prelabeled with [3H]-dopamine (DA). Verapamil (50 pM) 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 Ca" dependent. Verapamil does not modify [3H]-NE baseline release, but increases dose dependently [3H]-5-HT and [3H]-DA baseline release. Verapamil(l0 pM, for 5 min) increases endogenous DA release (70%) and endogenous 5-HT release (40%) independently on the presence of external Ca" . 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 M) and [3H]-SCH-23390 specific binding (Ki of 9 x M) from striatal synaptosomal membranes, and [3H]-5-HT specific binding (Ki of 3 X lo-' 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)], another mechanism probably mediated by presynaptic receptors underlies the effects of verapamil on DA and 5-HT release from discrete brain regions.