Characterization of the effect of monensin on gamma-amino-n-butyric acid release from isolated nerve terminals.
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.
Sitges
M
M
Departamento de Neuroquímica, Instituto Mexicano de Psiquiatría, México.
D000613:Aminobutyrates / Q000494:pharmacology; D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D008985:Monensin / Q000494:pharmacology*; D009411:Nerve Endings / Q000378:metabolism*; D009994:Osmolar Concentration; D012964:Sodium / Q000494:pharmacology; D013574:Synaptosomes / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D014702:Veratrine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000613:Aminobutyrates; D000621:Aminoisobutyric Acids; C100049:2-aminoisobutyric acid; C005959:2,4-diaminobutyric acid; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D008985:Monensin; D012964:Sodium; D014700:Verapamil; D014702:Veratrine; D002118:Calcium