Enhancement of sphingosine 1-phosphate-induced phospholipase C activation during G(0)-G(1) transition in rat hepatocytes.
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 Ca(2+) 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 G(0)-G(1) 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.
Im
Dong-Soon
DS
Laboratory of Pharmacology, College of Pharmacy, Pusan National University, Pusan, Republic of Korea. imds@pusan.ac.kr
Tomura
Hideaki
H
Tobo
Masayuki
M
Tobe
Masayuki
M
Sato
Koichi
K
Okajima
Fumikazu
F
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D004247:DNA / Q000096:biosynthesis; D020536:Enzyme Activators / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects*; D006498:Hepatectomy; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D007295:Inositol Phosphates / Q000096:biosynthesis; D008115:Liver Regeneration / Q000187:drug effects; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D051381:Rats; D016192:Resting Phase, Cell Cycle / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D046509:Tissue Culture Techniques; D010738:Type C Phospholipases / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D020536:Enzyme Activators; D007295:Inositol Phosphates; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D004247:DNA; D010738:Type C Phospholipases; D013110:Sphingosine