初代培養肝実質細胞におけるセロトニンの増殖促進作用はMAPK/p70S6K経路を介している

• Published in: 日本薬理学会年会要旨集 p. 2-P-111
• Main Authors: 栗原, 一樹, 内藤, 浩太, 茂木, 肇, 木村, 光利, 荻原, 政彦
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2019
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.92.0_2-P-111

Previously, we reported that serotonin (5-hydoxytryptamine; 5-HT) induced DNA synthesis and proliferation in primary cultures of adult rat hepatocytes. The 5-HT effect was due to transforming growth factor (TGF)-α secreted by activation of 5-HT2B receptor/phospholipase C (PLC)/Ca2+ pathway. In this study, we investigated whether 5-HT would stimulate phosphorylation of ribosomal p70 S6 kinase (p70S6K) in the cultured cells. Phosphorylated p70S6K was identified by Western blotting analysis using anti-phospho-p70S6K monoclonal antibody. The phosphorylated p70S6K was increased at 5 min, and reached a peak at 30 min after 5-HT addition. On the other hand, the phosphorylation of p70S6K induced by 5-HT was completely abolished the 5-HT2B receptor antagonist, LY272015, U-73122, a PLC inhibitor, BAPTA/AM, a membrane-permeable Ca2+ chelator, verapamil, L-type Ca2+ channel blocker, and somatostatin. Moreover, specific inhibitors of growth-related signal transducers (e.g., LY294002, PD98059, and rapamycin) blocked phosphorylation of p70S6K induced by 5-HT. These results suggest that secretion of TGF-α accelerates hepatocyte proliferation through the mitogen-activated protein kinase (MAPK)/p70S6K pathway.