Molecular properties of amiloride action and of its Na+ transporting targets

Abstract

Benos in his 1982 review on amiloride concluded that the molecule would probably become 'a molecular probe for the ultimate understanding of many basic cellular functions.' The present review, which analyzes more recent literature, fully confirms this conclusion. Probably the most important observation made in recent years is that several Na+ transporting systems are sensitive to amiloride and can be distinguished according to their sensitivity to selected amiloride derivatives. It is clear now that amiloride derivatives such as ethylisopropylamiloride on one hand and benzamil and phenamil, on the other hand, are far more potent inhibitors than amiloride for inhibiting the Na+/H+ antiport and the epithelial Na+ channel, respectively. Undoubtedly they are essential tools for attempting the purification of both the Na+/H+ exchange system and the epithelial Na+ channel and for understanding their molecular mechanisms and their multiple regulations.