EXTRACELLULAR ATP PROMOTES CELLULAR GROWTH OF RENAL INNER MEDULLARY COLLECTING DUCT CELLS MEDIATED VIA P-2U RECEPTORS

The present study was undertaken to determine whether extracellular ad enosine 5'-triphosphate (ATP) promotes cellular proliferation of cultu red rat renal inner medullary collecting duct cells. Extracellular ATP increased inositol 1,415-triphosphate (IP3) production and cellular f ree calcium concentration - [Ca2+](i) - in a dose-dependent manner. AT P also caused a transient cellular acidification. Extracellular ATP ac tivated mitogen-activated protein (MAP) kinase and [H-3]thymidine inco rporation in a dose-dependent manner. However, such effects were not o btained with adenosine 5'-diphosphate. adenosine monophosphate, and ad enosine. 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 IPI production, but did not affect the MAP kinase activity, We also examined the effect of arginin e vasopressin on cellular growth. Arginine vasopressin did not alter M AP kinase activity and [H-3]thymidine incorporation in cultured rat re nal 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 mediate d through P-2u, purinergic receptors in renal inner medullary collecti ng duct cells.