Am J Physiol Renal Physiol 2006 Feb 01;2902:F417-27. doi: 10.1152/ajprenal.00395.2004.

PMA- and ANG II-induced PKC regulation of the renal Na+-HCO3- cotransporter (hkNBCe1).

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The renal electrogenic Na(+)-HCO3- cotransporter (hkNBCe1) plays a major role in the bicarbonate reabsorption by the kidney. We examined how PMA- and ANG II-activated PKCs regulate hkNBCe1 expressed with or without the ANG II receptors AT(1B) in Xenopus laevis oocytes. We found that 10 nM PMA halved the hkNBCe1 current detected in voltage-clamped oocytes. A PKC-specific inhibitor GF-109203X, and a specific inhibitor of Ca-dependent conventional PKCalphabetagamma, GO-6976, significantly reduced PMA inhibition. PMA did not alter surface expression of the cotransporters, but it significantly increased hkNBCe1-PKCalphabetagamma membrane association. We found that at 10(-6) M, ANG II halved the hkNBCe1 current detected in oocytes coexpressing cotransporters with AT(1B). A PKC-specific inhibitor GF-109203X, and a PKCepsilon translocation inhibitor epsilonV1-2 peptide as well as BAPTA-AM (but not GO-6976), significantly reduced ANG II inhibition. At 10(-6) M, ANG II significantly decreased surface expression of the cotransporters and increased hkNBCe1-PKCepsilon membrane association. Additionally, we found that at 10(-11) and 10(-10) M ANG II stimulated hkNBCe1 current. This effect was blocked by BAPTA-AM and partially reduced by GF-109203X. We also found that ANG II increased intracellular Ca2+ in fluo 4-loaded oocytes. Our results suggest that 1) PMA inhibition of hkNBCe1 is mediated by Ca-dependent PKCalphabetagamma and 10 nM PMA does not induce downregulation of cotransporter surface expression. 2) ANG II (10(-6) M) inhibition of hkNBCe1 is mediated by both Ca-independent PKCepsilon and downregulation of cotransporter surface expression, possibly triggered by intracellular Ca2+ mobilization. 3) Similar to proximal tubule, acute ANG II has a biphasic effect on hkNBCe1 coexpressed with AT(1B) in X. laevis oocytes.

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Species referenced: Xenopus laevis
Genes referenced: adm