title: Novel Schering and ouabain-insensitive potassium-dependent proton secretion in the mouse cortical collecting duct.
abstract: The intercalated (IC) cells of the cortical collecting duct (CCD) are important to acid-base homeostasis by secreting acid and reabsorbing bicarbonate. Acid secretion is mediated predominantly by apical membrane Schering (SCH-28080)-sensitive H(+)-K(+)- ATPase (HKA) and bafilomycin-sensitive H(+)-ATPase. The SCH-28080-sensitive HKA is believed to be the gastric HKA (HKAg). Here we examined apical membrane potassium-dependent proton secretion in IC cells of wild-type HKAg (+/+) and HKAg knockout (-/-) mice to determine relative contribution of HKAg to luminal proton secretion. The results demonstrated that HKAg (-/-) and wild-type mice had comparable rates of potassium-dependent proton secretion, with HKAg (-/-) mice having 100% of K(+)-dependent H(+) secretion vs. wild-type mice. Potassium-dependent proton secretion was resistant to ouabain and SCH-28080 in HKAg knockout mice but was sensitive to SCH-28080 in wild-type animals. Northern hybridizations did not demonstrate any upregulation of colonic HKA in HKAg knockout mice. These data indicate the presence of a previously unrecognized K(+)-dependent SCH-28080 and ouabain-insensitive proton secretory mechanism in the cortical collecting tubule that may play an important role in acid-base homeostasis.
authors.affiliation: Department of Medicine, University of Cincinnati, Cincinnati, Ohio 45267, USA.
authors.forename: Snezana
authors.initials: S
authors.lastname: Petrovic
authors.forename: Zachary
authors.initials: Z
authors.lastname: Spicer
authors.forename: Tracey
authors.initials: T
authors.lastname: Greeley
authors.forename: Gary E
authors.initials: GE
authors.lastname: Shull
authors.forename: Manoocher
authors.initials: M
authors.lastname: Soleimani
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000494:pharmacology*; D007672:Kidney Cortex / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010042:Ouabain / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011522:Protons; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011522:Protons; D012333:RNA, Messenger; C035235:Sch 28080; D010042:Ouabain; D017506:H(+)-K(+)-Exchanging ATPase; D011188:Potassium