Enhancement of Sphingosine 1-Phosphate-Induced Phospholipase C Activation During G₀-G₁ Transition in Rat Hepatocytes

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We previously reported that sphingosine 1-phosphate (S1P) 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 (G₀) phase to proliferating (G₁/S) phase in hepatocytes. By employing cell-density-dependency of the transition (G₀-G₁) 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 G₀-G₁ transition. The correlation was further confirmed in vivo by 70% hepatectomy as a proliferating hepatocytes model. Northern blot analysis suggested an enhanced expression of S1P₂ receptor in proliferating hepatocytes.