Regulation of glomerulotubular balance. I. Impact of dopamine on flow-dependent transport Academic Article uri icon

Overview

MeSH Major

  • Dopamine
  • Kidney Glomerulus
  • Kidney Tubules

abstract

  • In response to volume expansion, locally generated dopamine decreases proximal tubule reabsorption by reducing both Na/H-exchanger 3 (NHE3) and Na-K-ATPase activity. We have previously demonstrated that mouse proximal tubules in vitro respond to changes in luminal flow with proportional changes in Na(+) and HCO(3)(-) reabsorption and have suggested that this observation underlies glomerulotubular balance. In the present work, we investigate the impact of dopamine on the sensitivity of reabsorptive fluxes to changes in luminal flow. Mouse proximal tubules were microperfused in vitro at low and high flow rates, and volume and HCO(3)(-) reabsorption (J(v) and J(HCO3)) were measured, while Na(+) and Cl(-) reabsorption (J(Na) and J(Cl)) were estimated. Raising luminal flow increased J(v), J(Na), and J(HCO3) but did not change J(Cl). Luminal dopamine did not change J(v), J(Na), and J(HCO3) at low flow rates but completely abolished the increments of Na(+) absorption by flow and partially inhibited the flow-stimulated HCO(3)(-) absorption. The remaining flow-stimulated HCO(3)(-) absorption was completely abolished by bafilomycin. The DA1 receptor blocker SCH23390 and the PKA inhibitor H89 blocked the effect of exogenous dopamine and produced a two to threefold increase in the sensitivity of proximal Na(+) reabsorption to luminal flow rate. Under the variety of perfusion conditions, changes in cell volume were small and did not always parallel changes in Na(+) transport. We conclude that 1) dopamine inhibits flow-stimulated NHE3 activity by activation of the DA1 receptor via a PKA-mediated mechanism; 2) dopamine has no effect on flow-stimulated H-ATPase activity; 3) there is no evidence of flow stimulation of Cl(-) reabsorption; and 4) the impact of dopamine is a coordinated modulation of both luminal and peritubular Na(+) transporters.

publication date

  • August 2012

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3433864

Digital Object Identifier (DOI)

  • 10.1152/ajprenal.00531.2011

PubMed ID

  • 22552936

Additional Document Info

start page

  • F386

end page

  • 95

volume

  • 303

number

  • 3