Apical extracellular calcium/polyvalent cation-sensing receptor regulates vasopressin-elicited water permeability in rat kidney inner medullary collecting duct

J Clin Invest. 1997 Mar 15;99(6):1399-405. doi: 10.1172/JCI119299.


During antidiuresis, increases in vasopressin (AVP)-elicited osmotic water permeability in the terminal inner medullary collecting duct (tIMCD) raise luminal calcium concentrations to levels (> or = 5 mM) above those associated with the formation of calcium-containing precipitates in the urine. Calcium/polycation receptor proteins (CaRs) enable cells in the parathyroid gland and kidney thick ascending limb of Henle to sense and respond to alterations in serum calcium. We now report the presence of an apical CaR in rat kidney tIMCD that specifically reduces AVP-elicited osmotic water permeability when luminal calcium rises. Purified tIMCD apical membrane endosomes contain both the AVP-elicited water channel, aquaporin 2, and a CaR. In addition, aquaporin 2-containing endosomes also possess stimulatory (G(alpha q)/G(alpha 11) and inhibitory (G(alpha i1, 2, and 3)) GTP binding proteins reported previously to interact with CaRs as well as two specific isoforms (delta and zeta) of protein kinase C. Immunocytochemistry using anti-CaR antiserum reveals the presence of CaR protein in both rat and human collecting ducts. Together, these data provide support for a unique tIMCD apical membrane signaling mechanism linking calcium and water metabolism. Abnormalities in this mechanism could potentially play a role in the pathogenesis of renal stone formation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / physiology*
  • Cations
  • Cell Membrane Permeability / drug effects*
  • Epithelium / chemistry
  • Epithelium / physiology
  • Extracellular Space / physiology
  • Immunoblotting
  • Immunohistochemistry
  • Kidney Medulla / chemistry
  • Kidney Medulla / physiology
  • Kidney Tubules, Collecting / chemistry
  • Kidney Tubules, Collecting / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Calcium-Sensing
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / physiology*
  • Vasopressins / pharmacology*
  • Water / metabolism*


  • Cations
  • Receptors, Calcium-Sensing
  • Receptors, Cell Surface
  • extracellular calcium cation-sensing receptor, rat
  • Water
  • Vasopressins
  • Calcium