Characterization of the Effect of Monensin on γ-Amino-n-Butyric Acid Release from Isolated Nerve Terminals |
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Authors: | María Sitges |
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Institution: | Departamento de Neuroquímica, Instituto Mexicano de Psiquiatría, México. |
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Abstract: | 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. |
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Keywords: | Synaptosomes Release γ-Amino-n-butyric acid Homoexchange Uptake Monensin Tetrodotoxin Verapamil |
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