title: Loss of acidification of anterior prostate fluids in Atp12a-null mutant mice indicates that nongastric H-K-ATPase functions as proton pump in vivo.
abstract: The physiological functions of nongastric (colonic) H-K-ATPase (gene symbol Atp12a), unlike those of Na-K-ATPase and gastric H-K-ATPase, are poorly understood. It has been suggested that it pumps Na+ more efficiently than H+; however, so far, there is no direct evidence that it pumps H+ in vivo. Previously, we found that the nongastric H-K-ATPase alpha-subunit is expressed in apical membranes of rodent anterior prostate epithelium, in a complex with the Na-K-ATPase beta1-subunit. Here we report the effects of Atp12a gene ablation on polarization of the beta1-subunit and secretory function of the anterior prostate. In nongastric H-K-ATPase-deficient prostate, the Na-K-ATPase alpha-subunit resided exclusively in basolateral membranes; however, the beta1-subunit disappeared from apical membranes, demonstrating that beta1 is an authentic subunit of nongastric H-K-ATPase in vivo and that apical localization of beta1 in the prostate is completely dependent on its association with the nongastric H-K-ATPase alpha-subunit. A remarkable reduction in acidification of anterior prostate fluids was observed: pH 6.38 +/- 0.14 for wild-type mice and 6.96 +/- 0.10 for homozygous mutants. These results show that nongastric H-K-ATPase is required for acidification of luminal prostate fluids, thereby providing a strong in vivo correlate of previous functional expression studies demonstrating that it operates as a proton pump.
authors.affiliation: Dept. of Physiology, Pharmacology, Metabolism, and Cardiovascular Sciences, Med. Univ. of Ohio, 3035 Arlington Ave., Toledo, OH 43614, USA.
authors.forename: Nikolay B
authors.initials: NB
authors.lastname: Pestov
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Korneenko
authors.forename: Mikhail I
authors.initials: MI
authors.lastname: Shakhparonov
authors.forename: Gary E
authors.initials: GE
authors.lastname: Shull
authors.forename: Nikolai N
authors.initials: NN
authors.lastname: Modyanov
mesh_terms: D000818:Animals; D017506:H(+)-K(+)-Exchanging ATPase / Q000737:chemistry / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism*; D017494:Proton Pumps / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000201:enzymology*
chemical_list: C478382:Atpaf2 protein, mouse; D018832:Molecular Chaperones; D017494:Proton Pumps; D025261:Mitochondrial Proton-Translocating ATPases; D017506:H(+)-K(+)-Exchanging ATPase