title: Increased CO(2) stimulates K/Rb reabsorption mediated by H-K-ATPase in CCD of potassium-restricted rabbit.
abstract: Apical H-K-ATPase in the cortical collecting duct (CCD) plays an important role in urinary acidification and K reabsorption. Our previous studies demonstrated that an H-K-ATPase mediates, in part, Rb reabsorption in rabbit CCD (Zhou X and Wingo CS. Am J Physiol Renal Fluid Electrolyte Physiol 263: F1134-F1141, 1992). The purpose of these experiments was to examine using in vitro microperfused CCD from K-restricted rabbits 1) whether an acute increase in PCO(2) and, presumably, intracellular acidosis stimulate K absorptive flux; and 2) whether this stimulation was dependent on the presence of a functional H-K-ATPase. Rb reabsorption was significantly increased after exposure to 10% CO(2) in CCD, and this effect was persistent for the entire 10% CO(2) period, whereas 10 microM SCH-28080 in the perfusate totally abolished the stimulation of Rb reabsorption by 10% CO(2). After stimulation of Rb reabsorption by 10% CO(2), subsequent addition of 0.1 mM methazolamide, an inhibitor of carbonic anhydrase, failed to affect Rb reabsorption. However, simultaneous exposure to 10% CO(2) and methazolamide prevented the stimulation of Rb reabsorption. Treatment with the intracellular calcium chelator MAPTAM (0.5 microM) inhibited the stimulation of Rb reabsorption by 10% CO(2). Similar inhibition was also observed in the presence of either a calmodulin inhibitor, W-7 (0.5 microM), or colchicine (0.5 mM), an inhibitor of tubulin polymerization. In time control studies, the perfusion time did not significantly affect Rb reabsorption. We conclude the following: 1) stimulation of Rb reabsorption on exposure to 10% CO(2) is dependent on the presence of a functional H-K-ATPase and appears to be regulated in part by the insertion of this enzyme into the apical plasma membrane by exocytosis; 2) insertion of H-K-ATPase requires changes in intracellular pH and needs a basal level of intracellular calcium concentration; and 3) H-K-ATPase insertion occurs by a microtubule-dependent process.
authors.affiliation: Division of Nephrology, Hypertension and Transplantation, Department of Medicine, College of Medicine, University of Florida, 32608-1197, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.forename: S L
authors.initials: SL
authors.lastname: Xia
authors.forename: C S
authors.initials: CS
authors.lastname: Wingo
mesh_terms: D000042:Absorption; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D003078:Colchicine / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006074:Gout Suppressants / Q000494:pharmacology; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D008704:Methazolamide / Q000494:pharmacology; D010477:Perfusion; D011188:Potassium / Q000378:metabolism*; D054328:Proton Pump Inhibitors; D011817:Rabbits; D012413:Rubidium / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D002614:Chelating Agents; D004232:Diuretics; D004791:Enzyme Inhibitors; D006074:Gout Suppressants; D007093:Imidazoles; D054328:Proton Pump Inhibitors; D013449:Sulfonamides; C035235:Sch 28080; D002245:Carbon Dioxide; D004533:Egtazic Acid; C017967:W 7; C058180:5,5'-dimethyl-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate; D017506:H(+)-K(+)-Exchanging ATPase; D012413:Rubidium; D011188:Potassium; D003078:Colchicine; D008704:Methazolamide