Effect of ouabain on the gamma-[3H]aminobutyric acid uptake and release in the absence of Ca(+)+ and K(+)-depolarization.
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.
Santos
M S
MS
Department of Zoology, University of Coimbra, Codex, Portugal.
Gonçalves
P P
PP
Carvalho
A P
AP
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D008564:Membrane Potentials / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology*; D012756:Sheep; D012965:Sodium Chloride / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000493:pharmacokinetics*
D014316:Tritium; D012965:Sodium Chloride; D005680:gamma-Aminobutyric Acid; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase