Extracellular purines’ action on glomerular albumin permeability in isolated rat glomeruli: Insights into the pathogenesis of albuminuria

Academic Article

Abstract

  • Purinoceptors (adrengeric receptors and P2 receptors) are expressed on the cellular components of the glomerular filtration barrier, and their activation may affect glomerular permeability to albumin, which may ultimately lead to albuminuria, a well-established risk factor for the progression of chronic kidney disease and development of cardiovascular diseases. We investigated the mechanisms underlying the in vitro and in vivo purinergic actions on glomerular filter permeability to albumin by measuring convectional albumin permeability (P ) in a single isolated rat glomerulus based on the video microscopy method. Primary cultured rat podocytes were used for the analysis of P , cGMP accumulation, PKG-Iα dimerization, and immunofluorescence. In vitro, natural nucleotides (ATP, ADP, UTP, and UDP) and nonmetabolized ATP analogs (2-meSATP and ATP-ϓ-S) increased P in a time- and concentration-dependent manner. The effects were dependent on P2 receptor activation, nitric oxide synthase, and cytoplasmic guanylate cyclase. ATP analogs significantly increased P , cGMP accumulation, and subcortical actin reorganization in a PKG-dependent but nondimer-mediated route in cultured podocytes. In vivo, 2-meSATP and ATP-ϓ-S increased P but did not significantly affect urinary albumin excretion. Both agonists enhanced the clathrin-mediated endocytosis of albumin in podocytes. A product of adenine nucleotides hydrolysis, adenosine, increased the permeability of the glomerular barrier via adrenergic receptors in a dependent and independent manner. Our results suggest that the extracellular nucleotides that stimulate an increase of glomerular P involve nitric oxide synthase and cytoplasmic guanylate cyclase with actin reorganization in podocytes. alb alb alb alb alb alb
  • Digital Object Identifier (doi)

    Author List

  • Kasztan M; Piwkowska A; Kreft E; Rogacka D; Audzeyenka I; Szczepanska-Konkel M; Jankowski M
  • Start Page

  • F103
  • End Page

  • F111
  • Volume

  • 311
  • Issue

  • 1