P2Y Receptors Regulate Proliferation of Human Pancreatic Duct Epithelial Cells

Abstract

The aim of this study was to investigate the effect of P2Y receptor activation on proliferation of human pancreatic duct epithelial cells. Proliferation was measured by immunoassay for bromodeoxyuridine incorporation into a pancreatic duct epithelial cell line, PANC-1. Expression of P2Y receptors was examined using quantitative reverse transcription-polymerase chain reaction and Western blot. Extracellular nucleotides, adenosine diphosphate (ADP) and uridine diphosphate (UDP), stimulated proliferation of pancreatic duct cells in a concentration-dependent manner. The nucleotide efficacy order was ADP > UDP > uridine triphosphate (UTP) > adenosine triphosphate. P2Y(1) and P2Y(6) receptor blockers, MRS2500 and MRS2578, blocked the effect of ADP and UDP. The signal that transmitted the proliferative activity of ADP and UDP was transducted to phospholipase C, inositol 1,4,5-triphosphate receptor, and protein kinase C. These results indicate involvement of P2Y(1) and P2Y(6) receptors in ADP- and UDP-stimulated proliferation. Pancreatic duct cells expressed the messenger RNA transcripts of P2Y receptors, P2Y(1) , P2Y(2), and P2Y(6), and P2Y(1) and P2Y(6) receptor protein. Extracellular nucleotides increase proliferation of human pancreatic duct epithelial cells by activation of P2Y(1) and P2Y(6) receptors. This provides the basic model for the effect of P2Y receptors on the proliferation of pancreatic duct epithelial cells.