Cellular origin and hormonal regulation of K⁺-ATPase activities sensitive to Sch-28080 in rat collecting duct

Abstract

Rat collecting ducts exhibit type I or type III K(+)-ATPase activities when animals are fed a normal (NK) or a K(+)-depleted diet (LK). This study aimed at determining functionally the cell origin of these two K(+)-ATPases. For this purpose, we searched for an effect on K(+)-ATPases of hormones that trigger cAMP production in a cell-specific fashion. The effects of 1-deamino-8-D-arginine vasopressin (dD-AVP), calcitonin, and isoproterenol in principal cells, alpha-intercalated cells, and beta-intercalated cells of cortical collecting duct (CCD), respectively, and of dD-AVP and glucagon in principal and alpha-intercalated cells of outer medullary collecting duct (OMCD), respectively, were examined. In CCDs, K(+)-ATPase was stimulated by calcitonin and isoproterenol in NK rats (type I K(+)-ATPase) and by dD-AVP in LK rats (type III K(+)-ATPase). In OMCDs, dD-AVP and glucagon stimulated type III but not type I K(+)-ATPase. These hormone effects were mimicked by the cAMP-permeant analog dibutyryl-cAMP. In conclusion, in NK rats, cAMP stimulates type I K(+)-ATPase activity in alpha- and beta-intercalated CCD cells, whereas in LK rats it stimulates type III K(+)-ATPase in principal cells of both CCD and OMCD and in OMCD intercalated cells.

CREB trans-activates the murine H+-K+-ATPase α2-subunit gene

“…2 gene expression in mIMCD-3 cells. cAMP and the adenylate cyclase agonist forskolin have been shown to rapidly activate H ϩ -K ϩ -ATPase activity in the rat OMCD via posttranslational mechanisms (15,16), but the ability of PKA-dependent activation of HK␣ 2 gene expression has not been studied. Vasopressin is a physiological agonist of cAMP/PKA and is known to act in this manner in the renal collecting duct.…”

“…Hormone signaling through cAMP/protein kinase A has been shown to rapidly stimulate type III K ϩ -ATPase in principal cells of both CCD and OMCD and in OMCD intercalated cells in K ϩ -depleted rats (15). To date, chronic effects of cAMP/protein kinase A on K ϩ -ATPase activity have not been demonstrated.…”

“…A third activity (type III) is activated by either Na ϩ or K ϩ and exhibits higher sensitivities than type II activity to ouabain and Sch-28080 and a lower sensitivity than type I activity to Sch-28080. This activity is not expressed basally but is specifically upregulated in cortical collecting ducts (CCD) and outer medullary collecting ducts (OMCD) with chronic hypokalemia (15) and thus may represent the functional correlate of HK␣ 2 .…”

Renal Vacuolar H+-ATPase

“…In contrast, ammonia (NH 3 ) and ammonium (NH 4 ϩ ) are produced in the proximal tubule by the metabolism of glutamine and glutamate, which in turn generates newly formed bicarbonate ions (373) 533,570), and the inhibition of proton secretion by the SCH28080 compound, a selective inhibitor of H ϩ -K ϩ -ATPase activity (200,569). It has, however, remained controversial to what extent the colonic, gastric, or both isoforms of H ϩ -K ϩ -ATPase underlie this activity as the use of pharmacological tools (ouabain, SCH28080, or omeprazole) and attempts to identify the molecular nature (immunohistochemistry, Northern, in situ hybridization) have produced partially conflicting data (95,163,164,200,291,296,374,375,551). It has, however, emerged that the contribution of H ϩ -K ϩ -ATPases to overall proton secretion in this segment and thus to bicarbonate reabsorption is minor and that H ϩ -K ϩ -ATPases may rather play an important role as a potassium scavenging pathway in systemic potassium depletion (20,144,199,216).…”

“…In addition to its direct effects on body calcium, calcitonin also increases bicarbonate reabsorption in the cortical collecting duct by stimulating H ϩ -ATPases in type A intercalated cells (123,464). Also, a stimulatory effect on H ϩ -K ϩ -ATPase has been reported (296). Under these circumstances, calcitonin would help prevent loss of bone by directly stimulating bone formation, reducing renal Ca 2ϩ loss, and counteracting metabolic acidosis by increasing acid secretion and bicarbonate generation.…”