Glenn M Toney1, Volker Vallon, James D Stockand. 1. Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA.
Abstract
PURPOSE OF REVIEW: This review summarizes the new evidence for an intrinsic control system in the aldosterone-sensitive distal nephron in which purinergic signaling regulates sodium transport and governs renal sodium excretion. RECENT FINDINGS: Electrophysiological studies identify epithelial Na(+) channels (ENaC) as final effectors of purinergic signaling via P2Y(2) receptors in the distal nephron. Inhibition of ENaC by autocrine/paracrine purinergic signaling reduces sodium reabsorption allowing an appropriately graded pressure-natriuresis response when delivery of sodium to the distal nephron is high. Disruption of this intrinsic control mechanism decreases sodium excretion and therefore has a prohypertensive effect. Because purinergic inhibition of ENaC is tonic yet submaximal, its enhancement increases sodium excretion and therefore has an antihypertensive action. SUMMARY: Purinergic inhibitory regulation of ENaC is a key component of an intrinsic control system that enables the distal nephron to respond appropriately to the delivered load of sodium. This control system is physiologically important and functions in parallel with extrinsic control by the renin-angiotensin-aldosterone system, enabling sodium excretion to keep pace with sodium intake, especially when intake is high, and thereby maintaining arterial blood pressure. Disruption of intrinsic control of sodium transport by the distal nephron likely contributes to diseases such as arterial hypertension.
PURPOSE OF REVIEW: This review summarizes the new evidence for an intrinsic control system in the aldosterone-sensitive distal nephron in which purinergic signaling regulates sodium transport and governs renal sodium excretion. RECENT FINDINGS: Electrophysiological studies identify epithelial Na(+) channels (ENaC) as final effectors of purinergic signaling via P2Y(2) receptors in the distal nephron. Inhibition of ENaC by autocrine/paracrine purinergic signaling reduces sodium reabsorption allowing an appropriately graded pressure-natriuresis response when delivery of sodium to the distal nephron is high. Disruption of this intrinsic control mechanism decreases sodium excretion and therefore has a prohypertensive effect. Because purinergic inhibition of ENaC is tonic yet submaximal, its enhancement increases sodium excretion and therefore has an antihypertensive action. SUMMARY: Purinergic inhibitory regulation of ENaC is a key component of an intrinsic control system that enables the distal nephron to respond appropriately to the delivered load of sodium. This control system is physiologically important and functions in parallel with extrinsic control by the renin-angiotensin-aldosterone system, enabling sodium excretion to keep pace with sodium intake, especially when intake is high, and thereby maintaining arterial blood pressure. Disruption of intrinsic control of sodium transport by the distal nephron likely contributes to diseases such as arterial hypertension.
Authors: Timo Rieg; Richard A Bundey; Yu Chen; George Deschenes; Wolfgang Junger; Paul A Insel; Volker Vallon Journal: FASEB J Date: 2007-06-15 Impact factor: 5.191
Authors: J H Hansson; C Nelson-Williams; H Suzuki; L Schild; R Shimkets; Y Lu; C Canessa; T Iwasaki; B Rossier; R P Lifton Journal: Nat Genet Date: 1995-09 Impact factor: 38.330
Authors: Oleh Pochynyuk; Qiusheng Tong; Jorge Medina; Alain Vandewalle; Alexander Staruschenko; Vladislav Bugaj; James D Stockand Journal: J Gen Physiol Date: 2007-10 Impact factor: 4.086
Authors: Yue Zhang; Simon C Robson; Kaiya L Morris; Kristina M Heiney; Karen M Dwyer; Bellamkonda K Kishore; Carolyn M Ecelbarger Journal: Am J Physiol Renal Physiol Date: 2015-04-15
Authors: Elena Mironova; I Jeanette Lynch; Jonathan M Berman; Michelle L Gumz; James D Stockand; Charles S Wingo Journal: Am J Physiol Renal Physiol Date: 2017-02-08
Authors: Tiffany L Thai; Ling Yu; Douglas C Eaton; Billie Jean Duke; Otor Al-Khalili; Ho Yin Colin Lam; Heping Ma; Hui-Fang Bao Journal: Am J Physiol Renal Physiol Date: 2014-08-06
Authors: David G Warnock; Kristina Kusche-Vihrog; Antoine Tarjus; Shaohu Sheng; Hans Oberleithner; Thomas R Kleyman; Frederic Jaisser Journal: Nat Rev Nephrol Date: 2014-01-14 Impact factor: 28.314
Authors: Yue Zhang; János Peti-Peterdi; Kristina M Heiney; Anne Riquier-Brison; Noel G Carlson; Christa E Müller; Carolyn M Ecelbarger; Bellamkonda K Kishore Journal: Purinergic Signal Date: 2015-09-19 Impact factor: 3.765
Authors: Vladislav Bugaj; Steven C Sansom; Donghai Wen; Lori I Hatcher; James D Stockand; Elena Mironova Journal: J Biol Chem Date: 2012-09-21 Impact factor: 5.157