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 [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.
Sitges
M
M
Departamento de Biología Molecular, Instituto de Investigaciones Biomédicas, UNAM, México D.F.
Reyes
A
A
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D015306:Biogenic Monoamines / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D066298:In Vitro Techniques; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*
D001552:Benzazepines; D015306:Biogenic Monoamines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017661:Receptors, Presynaptic; D011985:Receptors, Serotonin; D015102:3,4-Dihydroxyphenylacetic Acid; D013134:Spiperone; D014700:Verapamil; D011188:Potassium; D004298:Dopamine