Mineralocorticoids stimulate the activity and expression of renal H+,K+-ATPases.

ABSTRACT: In the renal collecting duct, mineralocorticoids drive Na(+) reabsorption, K(+) secretion, and H(+) secretion through coordinated actions on apical and basolateral transporters. Whether mineralocorticoids act through H(+),K(+)-ATPases to maintain K(+) and acid-base homeostasis is unknown. Here, treatment of mice with the mineralocorticoid desoxycorticosterone pivalate (DOCP) resulted in weight gain, a decrease in blood [K(+)] and [Cl(-)], and an increase in blood [Na(+)] and [HCO(3)(-)]. DOCP treatment increased the rate of H(+),K(+)-ATPase-mediated H(+) secretion in intercalated cells of the inner cortical collecting duct. mRNA expression of the catalytic subunit HK?(1) did not significantly change, whereas HK?(2) mRNA expression dramatically increased in the outer and inner medulla of DOCP-treated mice. A high-K(+) diet abrogated this increase in renal HK?(2) expression, showing that DOCP-mediated stimulation of HK?(2) expression depends on dietary K(+) intake. DOCP treatment of mice lacking HK?(1) (HK?(1)(-/-)) resulted in greater urinary Na(+) retention than observed in either wild-type mice or mice lacking both HK?(1) and HK?(2) (HK?(1,2)(-/-)). DOCP-treated HK?(1,2)(-/-) mice exhibited a lower blood [HCO(3)(-)] and less Na(+) and K(+) retention than either wild-type or HK?(1)(-/-) mice. Taken together, these results indicate that H(+),K(+)-ATPases-especially the HK?(2)-containing H(+),K(+)-ATPases-play an important role in the effects of mineralocorticoids on K(+), acid-base, and Na(+) balance.

SUBMITTER: Greenlee MM 

PROVIDER: S-EPMC3014034 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature