2‐Aminoperimidine, a specific inhibitor of bacterial NhaA Na+/H+ antiporters

Publisher Website
Google Scholar
Abstract
The diuretic drug amiloride and its numerous derivatives are competitive inhibitors of mammalian Na + /H + antiporters and other eukaryotic antiporters. Most prokaryotic antiporters, including the major NhaA family of enterobacteria, are resistant to these compounds. We show that 2-aminoperimidine (AP), a guanidine-containing naphthalene derivative with some similarity to amiloride, acts as a specific inhibitor of NhaA from Escherichia coli . Similar concentrations (IC 50 of 0.9 μM) inhibit the proton motive force dependent Na + (Li + )/H + exchange reaction in inside-out sub-bacterial vesicles (at 10 mM NaCl, pH 8) as well as the initial rate of 22 Na + /Na + exchange mediated by pure NhaA in proteoliposomes. The inhibitor is specific to NhaA type antiporters, so AP is a new tool to study the mechanism and roles of NhaA antiporters of enterobacteria as well as the molecular basis of inhibition by an amiloride-like compound.