PROTON ATPASES AND URINARY ACIDIFICATION

Acidification of the urine is mediated by vectorial H+ transport from cells at a number of sites in the kidney. A proton ATPase has been des cribed that appears to mediate a significant proportion of this H+ tra nsport. In particular, in proximal tubule and collecting duct, there i s evidence both for the presence of transporter protein and for H+ tra nsport with features that have been identified with it. This review hi ghlights some of the unresolved questions regarding this transporter, specifically, its distribution and relationship to the vacuolar pump p resent in endocytotic vesicles, how physiologic control is asserted, a nd its role in pathophysiology. The review discusses in greater detail the issue of whether the vacuolar H+ ATPase is responsible for all of the urinary acidification and concludes that it probably is not. Spec ifically, compelling evidence for acidification at sites in the kidney that appear to lack this transporter is presented. In addition, the e vidence for the presence in the kidney of a gastric-type H+-K+ ATPase is also reviewed. The evidence appears to be strong for a K+-stimulate d ATPase that is sensitive to omeprazole and SCH 28080, the prototypic al H+-K+ ATPase inhibitors; however, uncertainties remain because of p roblems of transport inhibition specificity and discordant results of molecular biologic studies.