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.