title: 2-Aminoperimidine, a specific inhibitor of bacterial NhaA Na(+)/H(+) antiporters.
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 muM) 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.
authors.affiliation: Department of Microbiology, University of Manitoba, Winnipeg, Man., Canada R3T 2N2. dibrovp@ms.umanitoba.ca
authors.forename: Pavel
authors.initials: P
authors.lastname: Dibrov
authors.forename: Abraham
authors.initials: A
authors.lastname: Rimon
authors.forename: Judith
authors.initials: J
authors.lastname: Dzioba
authors.forename: Arthur
authors.initials: A
authors.lastname: Winogrodzki
authors.forename: Yechiel
authors.initials: Y
authors.lastname: Shalitin
authors.forename: Etana
authors.initials: E
authors.lastname: Padan
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives; D002462:Cell Membrane / Q000502:physiology; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors*; D011510:Proteolipids / Q000187:drug effects / Q000502:physiology; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*
chemical_list: C114362:2-aminoperimidine; D029968:Escherichia coli Proteins; C102839:NhaA protein, E coli; D011510:Proteolipids; D011799:Quinazolines; D017923:Sodium-Hydrogen Exchangers; C020485:proteoliposomes; D000584:Amiloride; D012964:Sodium