Enhancement of sphingosine 1-phosphate-induced phospholipase C activation during G0-G1 transition in rat hepatocytes

We previously reported that sphingosine 1-phosphate (SIP) induces inhibition of adenylyl cyclase and activation of phospholipase C via independent G protein-coupled receptors in adult rat hepatocytes. Although S1P activation of phospholipase C and subsequent increase of intracellular Ca2+ concentration were enhanced during the primary culture of hepatocytes, S1P inhibition of adenylyl cyclase remained unchanged. Here, we addressed whether enhancement of S1P-induced actions is dependent on change of status from the differentiated (G(0)) phase to proliferating (G(1)/S) phase in hepatocytes. By employing cell-density-dependency of the transition (G(0)-G(1)) of hepatocytes in primary culture in vitro, it was found that the enhancement of phospholipase C activation by S1P was dependent on cell density and correlated to the GO-G, transition. The correlation was further confirmed in vivo by 70% hepatectomy as a proliferating hepatocytes model. Northern blot analysis suggested an enhanced expression of S1P(2) receptor in proliferating hepatocytes.