monensin and 2-4-diaminobutyric-acid

The action of the polyether antibiotic monensin on the release of gamma-[3H]amino-n-butyric acid [( 3H]GABA) from mouse brain synaptosomes is characterized. Monensin enhances the release of this amino acid transmitter in a dose-dependent manner and does not modify the efflux of the nontransmitter amino acid alpha-[3H]aminoisobutyrate. The absence of external Ca2+ fails to prevent the stimulatory effect of monensin on [3H]GABA release. Furthermore, monensin is less effective in stimulating [3H]GABA release in the presence of Ca2+. The releasing response to monensin is absolutely dependent on external Na+. The blockade of voltage-sensitive Na+ or Ca2+ channels does not modify monensin-induced release of the transmitter. Also, the blockade of the GABA uptake pathway fails to prevent the stimulatory effect of monensin on [3H]GABA release. Although monensin markedly increases Na+ permeability in synaptosomes, these data indicate that the Ca2+-independent monensin-stimulated transmitter release is not mediated by the Na+-dependent uptake pathway. It is concluded that the entrance of Na+ through monensin molecules inserted in the presynaptic membrane might be sufficient to initiate the intraterminal molecular events underlying transmitter release.

Topics: Aminobutyrates; Aminoisobutyric Acids; Animals; Calcium; gamma-Aminobutyric Acid; In Vitro Techniques; Mice; Mice, Inbred Strains; Monensin; Nerve Endings; Osmolar Concentration; Sodium; Synaptosomes; Tetrodotoxin; Verapamil; Veratrine

Topics: Amino Acids; Aminobutyrates; Animals; Biological Transport; Cations; Cell Membrane; Cerebral Cortex; gamma-Aminobutyric Acid; Gramicidin; Kinetics; Male; Monensin; Nigericin; Rats; Synaptosomes; Valinomycin