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 adenosine 5'-triphosphate (ATP) promotes cellular proliferation of cultured rat renal inner medullary collecting duct cells. Extracellular ATP increased inositol 1,415-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 [H-3]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 IPI 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 [H-3]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.