title: 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 HKα(1) did not significantly change, whereas HKα(2) mRNA expression dramatically increased in the outer and inner medulla of DOCP-treated mice. A high-K(+) diet abrogated this increase in renal HKα(2) expression, showing that DOCP-mediated stimulation of HKα(2) expression depends on dietary K(+) intake. DOCP treatment of mice lacking HKα(1) (HKα(1)(-/-)) resulted in greater urinary Na(+) retention than observed in either wild-type mice or mice lacking both HKα(1) and HKα(2) (HKα(1,2)(-/-)). DOCP-treated HKα(1,2)(-/-) mice exhibited a lower blood [HCO(3)(-)] and less Na(+) and K(+) retention than either wild-type or HKα(1)(-/-) mice. Taken together, these results indicate that H(+),K(+)-ATPases-especially the HKα(2)-containing H(+),K(+)-ATPases-play an important role in the effects of mineralocorticoids on K(+), acid-base, and Na(+) balance.
authors.affiliation: Research Service, North Florida/South Georgia Veterans Health System, 1601 SW Archer Road, Gainesville, FL 32608, USA.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Greenlee
authors.forename: I Jeanette
authors.initials: IJ
authors.lastname: Lynch
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Gumz
authors.forename: Brian D
authors.initials: BD
authors.lastname: Cain
authors.forename: Charles S
authors.initials: CS
authors.lastname: Wingo
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003900:Desoxycorticosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism*; D006859:Hydrogen / Q000097:blood; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008901:Mineralocorticoids / Q000494:pharmacology*; D011188:Potassium / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D012964:Sodium / Q000097:blood; D015430:Weight Gain / Q000187:drug effects / Q000502:physiology
chemical_list: D008901:Mineralocorticoids; D012333:RNA, Messenger; C019323:deoxycortone pivalate; D003900:Desoxycorticosterone; D006859:Hydrogen; D012964:Sodium; D017506:H(+)-K(+)-Exchanging ATPase; D011188:Potassium