5-(N-Ethyl-N-isopropyl)-amiloride inhibits amino acid release from the ischemic rat cerebral cortex: role of Na+-H+ exchange.
The effect of the selective Na+/H+ antiporter inhibitor 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) on amino acid release from the ischemic/reperfused rat cerebral cortex was investigated using a cortical cup technique. EIPA (25 microM in artificial cerebrospinal fluid), applied topically, inhibited the ischemia-reperfusion evoked efflux of aspartate, glutamate, gamma-aminobutyric acid, taurine and phosphoethanolamine. Reductions in the ischemia-evoked releases of these amino acids suggest that ischemia precipitates acidosis, Na+/H+ exchange and cell swelling with amino acid release as the cells mount a regulatory volume decrease response. EIPA, by blocking Na+/H+ exchange, would reduce cell swelling and the resulting amino acid release.
Phillis
J W
JW
Department of Physiology, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA. jphillis@med.wayne.edu
O'Regan
M H
MH
Song
D
D
D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*
D000596:Amino Acids; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; C039614:ethylisopropylamiloride