REGULATION OF COLONIC H-K-ATPASE IN LARGE-INTESTINE AND KIDNEY BY DIETARY NA DEPLETION AND DIETARY K DEPLETION

Active K absorption in the rat distal colon is energized by an apical membrane H-K-ATPase, whereas K absorption in the distal collecting duc t is generally believed to be modulated by a related renal H-K-ATPase. Experiments were performed to establish the mechanism(s) by which die tary Na depletion (with resulting elevated aldosterone levels) and K d epletion stimulate K absorption. A colonic H-K-ATPase-specific cDNA pr obe and a polyclonal antibody were utilized to measure mRNA (Northern blot analyses) and protein (Western blot and immunofluorescence studie s) abundance in the distal and proximal colon and renal collecting duc ts and cortex of dietary Na- and K-depleted rats. Dietary Na depletion , but not K depletion, upregulated H-K-ATPase-specific mRNA and protei n expression in the distal and proximal colon; Na depletion also stimu lated H-K-ATPase activity in the distal colon. In contrast to the dist al colon, H-K-ATPase-specific protein level in the outer medulla was e nhanced by dietary K depletion, but not by Na depletion. This study es tablishes that 1) dietary Na depletion stimulates colonic H-K-ATPase a ctivity most likely by a transcriptional process and 2) the regulation of colonic H-K-ATPase expression by dietary Na depletion and dietary Ti depletion is not identical in the large intestine and differs in th e kidney from the colon, suggesting the presence of two (or more) H-K- ATPase isoforms in the rat colon.