城西大学機関リポジトリJURAEffect of Selective Serotonin (5-HT)2B Receptor Agonist BW723C86 on Epidermal Growth Factor/Transforming Growth Factor-α Receptor Tyrosine Kinase and Ribosomal p70 S6 Kinase Activities in Primary Cultures of Adult Rat Hepatocytes

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Effect of Selective Serotonin (5-HT)2B Receptor Agonist BW723C86 on Epidermal Growth Factor/Transforming Growth Factor-α Receptor Tyrosine Kinase and Ribosomal p70 S6 Kinase Activities in Primary Cultures of Adult Rat Hepatocytes

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ID	JOS-bpb.b18-00831
著者：名前	内藤, 浩太/栗原, 一樹/茂木, 肇/木村, 光利/夏目, 秀視/荻原, 政彦
著者：別形式	Naito, Kota / Kurihara, Kazuki / Moteki, Hajime / Kimura, Mitsutoshi / Natsume, Hideshi / Ogihara, Masahiko
著者：カナ	ナイトウ, コウタ/クリハラ, カズキ/モテキ, ハジメ/キムラ, ミツトシ/ナツメ, ヒデシ/オギハラ, マサヒコ
著者：所属	城西大学薬学部臨床薬理学 / 城西大学薬学部臨床薬理学 / 城西大学薬学部臨床薬理学 / 城西大学薬学部臨床薬理学 / 城西大学薬学部製剤学 /城西大学薬学部臨床薬理学
著者：所属(別形式）	Josai University, Faculty of Pharmaceutical Sciences, Departments of Clinical Pharmacology / Josai University, Faculty of Pharmaceutical Sciences, Departments of Clinical Pharmacology / Josai University, Faculty of Pharmaceutical Sciences, Departments of Clinical Pharmacology / Josai University, Faculty of Pharmaceutical Sciences, Departments of Clinical Pharmacology / Josai University, Faculty of Pharmaceutical Sciences, Department of Pharmaceutics /Josai University, Faculty of Pharmaceutical Sciences, Departments of Clinical Pharmacology
著者版フラグ	publisher
出版地	東京
出版者	日本薬学会
出版者：カナ	ニホンヤクガクカイ
出版者：別名	The Pharmaceutical Society of Japan
NCID	AA10885497
冊子ISSN	09186158
電子ISSN	13475215
掲載誌名	Biological and Pharmaceutical Bulletin
巻	42
号	4
刊行年月	2019-04
開始ページ	631
終了ページ	637
コンテンツ作成日	2018-10-24
コンテンツ修正日	2019-01-07
コンテンツ登録日	2019-07-30
識別番号：DOI	info:doi/10.1248/bpb.b18-00831
識別番号：DOI（リンク）	https://doi.org/10.1248/bpb.b18-00831
PubMed番号	30713268
抄録	Serotonin (5-hydroxytryptamine; 5-HT) can induce hepatocyte DNA synthesis and proliferation by autocrine secretion of transforming growth factor (TGF)-α through 5-HT2B receptor/phospholipase C (PLC)/Ca2+ and a signaling pathway involving epidermal growth factor (EGF)/TGF-α receptor tyrosine kinase (RTK)/extracellular signal-regulated kinase 2 (ERK2)/mammalian target of rapamycin (mTOR). In the present study, we investigated whether 5-HT or a selective 5-HT2B receptor agonist BW723C86, would stimulate phosphorylation of TGF-α RTK and ribosomal p70 S6 kinase (p70S6K) in primary cultures of adult rat hepatocytes. Western blotting analysis was used to detect 5-HT- or BW723C86 (10−6 M)-induced phosphorylation of EGF/TGF-α RTK and p70S6K. Our results showed that 5-HT- or BW723C86 (10−6 M)-induced phosphorylation of EGF/TGF-α RTK peaked at between 5 and 10 min. On the other hand, 5-HT- or BW723C86 (10−6 M)-induced phosphorylation of p70S6K peaked at about 30 min. Furthermore, a selective 5-HT2B receptor antagonist LY272015, a specific PLC inhibitor U-73122, a membrane-permeable Ca2+ chelator BAPTA/AM, an L-type Ca2+ channel blocker verapamil, somatostatin, and a specific p70S6K inhibitor LY2584702 completely abolished the phosphorylation of p70S6K induced by both 5-HT and BW723C86. These results indicate that phosphorylation of p70S6K is dependent on the 5-HT2B-receptor-mediated autocrine secretion of TGF-α. In addition, these results demonstrate that the hepatocyte proliferating action of 5-HT and BW723C86 are mediated by phosphorylation of p70S6K, a downstream element of the EGF/TGF-α RTK signaling pathway.
キーワード	serotonin/signal transduction/ribosomal p70 S6 kinase (p70S6K)/transforming growth factor-α/proliferation (cultured hepatocyte)
言語	eng
資源タイプ	text
ジャンル	01学術雑誌論文 / Journal Article
フォーマット	application/pdf
権利	Copyright © 2019 The Pharmaceutical Society of Japan
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このアイテムを表示する：URI	http://libir.josai.ac.jp/il/meta_pub/G0000284repository_JOS-bpb.b18-00831

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