Amiloride inhibition of the Na+-H+ exchanger in renal microvillus membrane vesicles.
We examined the effect of amiloride on Na+-H+ exchange in rabbit renal cortical microvillus membrane vesicles. Amiloride inhibited both the uphill Na+ accumulation induced by imposition of a transmembrane Hin+ greater than Hout+ gradient and the uphill H+ efflux induced by imposition of a Naout+ greater than Nain+ gradient. The inhibitory effect of amiloride on Na+ influx was rapidly reversible and fully competitive (Ki 3.0 X 10(-5) M amiloride, KT 6.3 mM Na+). In addition, amiloride inhibited the efflux of Na+ from vesicles preloaded with Na+. However, the diuretic did not inhibit such other Na+-coupled transport processes as Na+-glucose ad Na+-alanine cotransport. These findings suggest that amiloride is a reversible, selective, competitive inhibitor for the Na+ site of the renal microvillus membrane Na+-H+ exchanger. Amiloride may, therefore, be useful as an experimental tool for investigating the role of Na+-H+ exchange in mediating proximal tubular acidification.
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001693:Biological Transport, Active; D005947:Glucose / Q000378:metabolism; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000648:ultrastructure*; D008871:Microvilli / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*
D001639:Bicarbonates; D011719:Pyrazines; D000584:Amiloride; D006859:Hydrogen; D012964:Sodium; D005947:Glucose