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Effect of ouabain on the gamma-[3H]aminobutyric acid uptake and release in the absence of Ca(+)+ and K(+)-depolarization

MS Santos, PP Goncalves and AP Carvalho

Department of Zoology, University of Coimbra, Codex, Portugal.

The effect of ouabain on the uptake of tritiated [3H]GABA and on its release in the absence of Ca(+)+ was studied in brain cortex synaptosomes. Ouabain, in the absence of Ca(+)+ and K(+)- depolarization, induces the release of [3H]GABA with half-maximal effect occurring at a concentration of about 7 X 10(-6) M. Parallel measurements of the effects of ouabain on the [3H]GABA uptake and the Na+,K(+)-adenosine triphosphatase activity show that ouabain inhibits both mechanisms and that the half-maximal effect also occurs at about the same ouabain concentration. Although [3H]GABA release is stimulated by ouabain, it appears that the inhibition of [3H]GABA uptake is due to a direct effect on the uptake mechanism, inasmuch as the initial velocity of the process is inhibited by ouabain. Ouabain requires extracellular Na+ for [3H]GABA release and for membrane depolarization and, in the absence of Na+, ouabain does not cause either [3H]GABA release or membrane depolarization. No significant changes in the Na+ gradients occur under conditions which permit release of [3H]GABA, but the Na+,K(+)-adenosine triphosphatase activity is inhibited, which may be responsible for membrane depolarization, which in turn may cause [3H]GABA release or inhibit its uptake.

Volume 253, Issue 2, pp. 620-627, 05/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics




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