title: Intrinsic control of sodium excretion in the distal nephron by inhibitory purinergic regulation of the epithelial Na(+) channel.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Toney
authors.forename: Volker
authors.initials: V
authors.lastname: Vallon
authors.forename: James D
authors.initials: JD
authors.lastname: Stockand
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001794:Blood Pressure; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D007686:Kidney Tubules, Distal / Q000378:metabolism* / Q000503:physiopathology; D008564:Membrane Potentials; D009318:Natriuresis; D011687:Purines / Q000378:metabolism*; D058473:Receptors, Purinergic P2Y2 / Q000378:metabolism*; D012084:Renin-Angiotensin System; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000378:metabolism
chemical_list: D053503:Epithelial Sodium Channels; D011687:Purines; D058473:Receptors, Purinergic P2Y2; D017673:Sodium Chloride, Dietary; D000450:Aldosterone; D012964:Sodium