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  • Title: 5-(N-ethyl-N-isopropyl)amiloride and mild acidosis protect cultured cerebellar granule cells against glutamate-induced delayed neuronal death.
    Author: Andreeva N, Khodorov B, Stelmashook E, Sokolova S, Cragoe E, Victorov I.
    Journal: Neuroscience; 1992 Jul; 49(1):175-81. PubMed ID: 1357585.
    Abstract:
    In the experiments on the primary cerebellar granule cell cultures, delayed neuronal death was induced by 15 min treatment of the cells with 50 microM glutamate. 5-(N-ethyl-N-isopropyl)amiloride (10 microM) known as a potent inhibitor of the Na+/H+ exchanger, when added to the glutamate-containing Mg(2+)-free solution caused a considerable (approximately by 40%) decrease in the number of dead cells counted 4 h after the termination of glutamate treatment. Patch-clamp experiments with freshly isolated rat hippocampal neurons have shown that the neuroprotective effect of 5-(N-ethyl-N-isopropyl)amiloride can be explained by its ability to block N-methyl-D-aspartate channels (receptors) at micromolar concentrations. A similar mechanism apparently underlies neuroprotective effect of external acidosis (reduction of pH from 7.6-7.8 to 6.7-6.8) during glutamate application. 5-(N-ethyl-N-isopropyl)amiloride (10 microM) and low pH (6.7) also proved capable of exhibiting neuroprotective effects upon application during the post-glutamate period. In this instance, however, the number of dead cells was decreased by no more than 20%. This neuroprotective effect of 5-(N-ethyl-N-isopropyl)amiloride and low pH is interpreted as resulting from inhibition of Na+/H+ exchange, since a direct blockade of N-methyl-D-aspartate receptors by 1 mM DL-2-amino-5-phosphonovalerate after termination of glutamate treatment did not attenuate the delayed neuronal death. Finally, we have established that the addition of 10 microM 5-(N-ethyl-N-isopropyl)amiloride to the cultures both during glutamate treatment and after its termination results in a complete protection of cultured cerebellar granule cells.
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