Regulation of the Proximal Tubule Vacuolar H+-ATPase by PKA and AMP-Activated Protein Kinase.

We examined the role of PKA and AMP-activated protein kinase (AMPK) in the regulation of the V-ATPase in the proximal tubule as these two kinases co-regulate the V-ATPase in the collecting duct. As the proximal tubule V-ATPases have different subunit compositions from other nephron segments, we postulated that V-ATPase regulation in the proximal tubule could differ from other kidney tubule segments. Immunofluorescence labeling of rat ex vivo kidney slices revealed that the V-ATPase was present in the proximal tubule both at the apical pole, co-localizing with the brush border marker wheat germ agglutinin, and in the cytosol when slices were incubated in buffer alone. When slices were incubated with a cAMP analog and a phosphodiesterase inhibitor, the V-ATPase accumulated at the apical pole of S3 segment cells. These PKA activators also increased V-ATPase apical membrane expression as well as the rate of V-ATPase-dependent extracellular acidification in S3 cell monolayers relative to untreated cells. However, the AMPK activator AICAR decreased PKA-induced V-ATPase apical accumulation in proximal tubules of kidney slices and decreased V-ATPase activity in S3 cell monolayers. Our results suggest that in proximal tubule the V-ATPase subcellular localization and activity are acutely co-regulated via PKA downstream of hormonal signals and via AMPK downstream of metabolic stress.
PMID: 24553431 [PubMed - as supplied by publisher]

Source: Am J Physiol Renal P... - February 19, 2014 Category: Urology & Nephrology Authors: Al-Bataineh MM, Gong F, Marciszyn A, Myerburg MM, Pastor-Soler NM Tags: Am J Physiol Renal Physiol Source Type: research