The effect of verapamil on GABA and dopamine release does not involve voltage-sensitive calcium channels.
The effect of verapamil, which belongs to the group of drugs collectively referred to as 'organic Ca2+ channel blockers', was investigated on the basal and stimulated release of the neurotransmitters dopamine and GABA in rat striatum synaptosomes. Verapamil inhibits the Na(+)-dependent release of GABA in response to depolarization with an IC50 of 25 microM, whereas it is unable to modify the Na2(+)-independent, Ca2(+)-dependent fraction of GABA release induced by high K+ depolarization. Verapamil does not modify the basal release of GABA but stimulates the basal release of dopamine in a dose-dependent manner (ED50 5 microM). This verapamil-induced outflow of dopamine is independent of Ca2+ and occurs in the presence of tetrodotoxin, indicating that it is not mediated by voltage-sensitive Ca2+ or Na+ channels of the presynaptic membrane. Dopamine release induced by verapamil is cumulative with that induced by depolarizing agents (high K+ or veratridine). As verapamil, pimozide, a neuroleptic of the diphenylbutylpiperidine type, increases the basal and stimulated release of dopamine. We conclude that the opposite effects of verapamil of GABA and dopamine release are due to differences in the releasable fractions of these 2 types of neurotransmitters. Besides, none of these effects are directly linked with the blockade of voltage-operated Ca2+ channels of the presynaptic membrane.
Sitges
M
M
Instituto de Investigaciones Biomédicas, U.N.A.M., México, D.F., México.
Chiu
L M
LM
Ramón de la Fuente
J
J
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology*; D014701:Veratridine / Q000494:pharmacology; D014702:Veratrine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D015220:Calcium Channels; D005680:gamma-Aminobutyric Acid; D014701:Veratridine; D014700:Verapamil; D014702:Veratrine; D004298:Dopamine