Effects of drugs on neurotransmitter release: experiments in vivo and in vitro.

Calcium ions play a fundamental role in the release of transmitters in the nervous system. Therefore, drugs capable of modifying Ca2+ transport are useful tools for studying the mechanisms of such release in vivo and in vitro. In this article the action of some of these drugs on motor behavior, as well as on Ca2+ uptake and neurotransmitter release in synaptosomes, is reviewed. Ruthenium red (RuR) inhibits Ca2+ uptake and transmitter release in synaptosomes, and produces flaccid paralysis when injected intraperitoneally (IP) and convulsions after intracranial administration. Drugs which stimulate the Ca2+-dependent transmitter release in synaptosomes, such as 4-aminopyridine, antagonize the paralysis produced by RuR. Lanthanum ions also inhibit Ca2+ uptake and neurotransmitter release in synaptosomes, but no paralysis was observed after La2+ IP injection. However, this cation blocks the binding of RuR to the presynaptic membrane, and prevents the RuR-induced paralysis. Veratridine and the Ca2+ chelator EGTA were used to demonstrate in synaptosomes that besides the Ca2+-dependent mechanism of release of the central inhibitory transmitter gamma-aminobutyric acid (GABA), there seems to be a strictly Na+-dependent process which is not shared by other transmitters such as acetylcholine or dopamine.