Extracellular ATP promotes cellular growth of renal inner medullary collecting duct cells mediated via P2u receptors

Nephron. 1997;76(2):208-14. doi: 10.1159/000190170.


The present study was undertaken to determine whether extracellular adenosine 5'-triphosphate (ATP) promotes cellular proliferation of cultured rat renal inner medullary collecting duct cells. Extracellular ATP increased inositol 1,4,5-triphosphate (IP3) production and cellular free calcium concentration - [Ca2+]i - in a dose-dependent manner. ATP also caused a transient cellular acidification. Extracellular ATP activated mitogen-activated protein (MAP) kinase and [3H]thymidine incorporation in a dose-dependent manner. However, such effects were not obtained with adenosine 5'-diphosphate, adenosine monophosphate, and adenosine. In addition, uridine triphosphate, a P(2u) purinergic agonist, increased IP3 production and activated MAP kinase. 2-Methylthio ATP, a P(2y) purinergic agonist, also increased IP3 production, but did not affect the MAP kinase activity. We also examined the effect of arginine vasopressin on cellular growth. Arginine vasopressin did not alter MAP kinase activity and [3H]thymidine incorporation in cultured rat renal inner medullary collecting duct cells. These results indicate that extracellular ATP activates phospholipase C mediated through P(2u) and P(2y) purinergic receptors and promotes cellular proliferation mediated through P(2u) purinergic receptors in renal inner medullary collecting duct cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology*
  • Animals
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cell Division / drug effects
  • Cells, Cultured
  • Hydrogen-Ion Concentration
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Kidney Medulla / cytology*
  • Kidney Medulla / drug effects
  • Kidney Medulla / physiology
  • Kidney Tubules, Collecting / cytology*
  • Kidney Tubules, Collecting / drug effects
  • Kidney Tubules, Collecting / physiology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P2 / physiology*
  • Receptors, Purinergic P2Y2
  • Staurosporine / pharmacology
  • Suramin / pharmacology
  • Uridine Triphosphate / pharmacology


  • P2ry2 protein, rat
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2Y2
  • Suramin
  • Inositol 1,4,5-Trisphosphate
  • Adenosine Triphosphate
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Staurosporine
  • Calcium
  • Uridine Triphosphate