Amiloride and the Na+/H+ exchanger protein:: Mechanism and significance of inhibition of the Na+/H+ exchanger (Review)

Amiloride and its derivatives are important tools for studying NHE-1, the ubiquitous isoform of the sodium/hydrogen exchanger protein family. Three residues in putative transmembrane domains TV and IX have been implicated in amiloride binding and several models of the proposed amiloride-binding site have been reported. Though it has been shown that sodium ions and amiloride molecules interact at unique regions of the NHE-1 protein, physiological experiments reveal a competitive relationship between the two under some circumstances. The two binding sites are thus on closely related but distinct regions on the protein.