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5-(N-ethyl-N-isopropyl)amiloride and Mild Acidosis Protect Cultured Cerebellar Granule Cells Against Glutamate-Induced Delayed Neuronal Death

5-(N-ethyl-N-isopropyl)amiloride and Mild Acidosis Protect Cultured Cerebellar Granule Cells Against Glutamate-Induced Delayed Neuronal Death

N Andreeva, B Khodorov, E Stelmashook, S Sokolova, E Cragoe Jr, I Victorov

Neuroscience. 1992 Jul;49(1):175-81.

PMID: 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1154252	5-(N-Ethyl-N-isopropyl)amiloride		1154-25-2	Price

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