Effects of the anion channel blocker DIDS on ouabain- and high K(+)-induced release of amino acids from the rat cerebral cortex.
Amino acid release from the rat cerebral cortex was analyzed using an in vivo cortical cup perfusion model. Topical applications of ouabain or high extracellular K(+) were used to mimic two dimensions of ischemic conditions which promote cell swelling and amino acid release. Ouabain (30 microM) induced significant releases of taurine, gamma-aminobutyric acid (GABA), aspartate, glutamate and phosphoethanolamine. The anion channel blocker, 4, 4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS; 1 mM), inhibited ouabain-induced release of all these amino acids except for glutamate. Exposure to high extracellular K(+) (75 mM) induced a delayed rise in the levels of taurine in the superfusates and an immediate increase in GABA levels. There were no significant releases of other amino acids. The release of taurine and GABA was sensitive to the blocking of anion channels with DIDS. Both ouabain- and high K(+)-induced taurine release is likely to be mediated by DIDS sensitive anion channels. The extracellular accumulation of the other amino acids, where insensitive to DIDS, may be mediated by mechanisms other than swelling-induced anion channels.
Estevez
A Y
AY
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Song
D
D
Phillis
J W
JW
O'Regan
M H
MH
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology*; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D000838:Anions / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D007473:Ion Channels / Q000037:antagonists & inhibitors; D008297:Male; D009994:Osmolar Concentration; D010042:Ouabain / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D000838:Anions; D007473:Ion Channels; D005680:gamma-Aminobutyric Acid; D010042:Ouabain; D011189:Potassium Chloride; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid