Mineralocorticoids Stimulate the Activity and Expression of Renal H+,K+-ATPases

作者：Greenlee Megan M; Lynch I Jeanette; Gumz Michelle L; Cain Brian D; Wingo Charles S^*

来源：Journal of the American Society of Nephrology, 2011, 22(1): 49-58.

DOI：10.1681/ASN.2010030311

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 [HCO3-]. 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 alpha(1) did not significantly change, whereas HK alpha(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 alpha(2) expression, showing that DOCP-mediated stimulation of HK alpha(2) expression depends on dietary K+ intake. DOCP treatment of mice lacking HK alpha(1) (HKa(1)(-/-)) resulted in greater urinary Na+ retention than observed in either wild-type mice or mice lacking both HK alpha(1) and HK alpha(2) (HK alpha(-/-)(1,2)). DOCP-treated HK alpha(-/-)(1,2) mice exhibited a lower blood [HCO3-] and less Na+ and K+ retention than either wild-type or HK alpha(-/-)(1) mice. Taken together, these results indicate that H+,K+-ATPases-especially the HK alpha(2)-containing H+,K+-ATPases-play an important role in the effects of mineralocorticoids on K+, acid-base, and Na+ balance.

• 出版日期2011-1