title: Effects of acetazolamide on Na+-HCO-3 cotransport in basolateral membrane vesicles isolated from rabbit renal cortex.
abstract: We evaluated the effects of acetazolamide on Na+-HCO3- cotransport in basolateral membrane vesicles isolated from the rabbit renal cortex. Na+ uptake stimulated by an imposed inward HCO3- gradient was not significantly reduced by 1.2 mM acetazolamide, indicating that acetazolamide does not directly inhibit Na+-HCO3- cotransport. 4,4'-Diisothiocyanostilbene-2,2'-disulfonate (DIDS)-sensitive Na+-base cotransport was found to be absolutely CO2/HCO3--dependent. We therefore tested whether acetazolamide-sensitive availability of HCO3- at the basolateral membrane could be rate-limiting for Na+-base cotransport under some conditions. In the presence of a CO2/HCO3- buffer system but absence of an initial HCO3- gradient, Na+ influx was stimulated fivefold by an outward NH4+ gradient. This stimulation of Na+ influx by an outward NH4+ gradient was inhibited greater than 75% by 0.6 mM acetazolamide, suggesting that acetazolamide blocked the ability of the NH4+ gradient to generate an inward HCO3- gradient. In the presence of an inward HCO3- gradient, Na+ influx was inhibited greater than 70% by an inward NH4+ gradient. This inhibition of Na+ influx was reduced to only 35% by 0.6 mM acetazolamide, suggesting that acetazolamide blocked the ability of NH4+ to collapse the inward HCO3- gradient. Similarly, Na+ influx in the presence of an inward HCO3- gradient was inhibited greater than 80% by an outward acetate gradient, and this inhibition was reduced to only 50% by acetazolamide. Thus, acetazolamide caused either inhibition or stimulation of Na+ uptake depending on the conditions with respect to pH and HCO3- gradients. The indirect interaction of acetazolamide with the basolateral membrane Na+-HCO3- cotransport system may be an important mechanism underlying inhibition of proximal tubule acid secretion by this agent.
authors.affiliation: Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: M
authors.initials: M
authors.lastname: Soleimani
authors.forename: P S
authors.initials: PS
authors.lastname: Aronson
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000085:Acetates / Q000494:pharmacology; D000086:Acetazolamide / Q000494:pharmacology*; D000641:Ammonia / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*; D027982:Sodium-Bicarbonate Symporters
chemical_list: D000085:Acetates; D001639:Bicarbonates; D002352:Carrier Proteins; D027982:Sodium-Bicarbonate Symporters; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D000641:Ammonia; D012964:Sodium; D000086:Acetazolamide; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid