Activation of Mitogen-Activated Protein Kinase by Hepatocyte Growth Factor Is Stimulated by Both α1- and β2-Adrenergic Agonists in Primary Cultures of Adult Rat Hepatocytes

Journal of Pharmacological Sciences

Hiroshi Okamoto¹  Masahiko Ogihara¹  Mitsutoshi Kimura¹ 

[1] Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Josai University, Japan

关键词: mitogen-activated protein kinase (MAPK);    hepatocyte growth factor (HGF);    α1- and β2-adrenergic agonists;    hepatocyte;    cross-talk;   

DOI  :  10.1254/jphs.FP0061192

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(49)Cited-By(6)We investigated the effects of α1- and β2-adrenergic agonists on hepatocyte growth factor (HGF)-stimulated mitogen-activated protein kinase (MAPK) isoforms in primary cultures of adult rat hepatocytes. Hepatocytes were isolated and cultured with HGF (5 ng/ml) and/or α- and β-adrenergic agonists. Phosphorylated MAPK isoforms (p42 and p44 MAPK) were detected by Western blotting analysis using anti-phospho-MAPK antibody. The results show that HGF increased phosphorylation of p42 MAPK by 2.2-fold within 3 min. The HGF-induced MAPK activation was abolished by AG1478 treatment (10−7 M). The MEK (MAPK kinase) inhibitor PD98059 (10−6 M) completely inhibited the HGF-dependent increase in MAPK activity. Phenylephrine (10−6 M) and metaproterenol (10−6 M) alone had no effect in the absence of HGF, but significantly increased p42 MAPK induction by HGF. Moreover, the cell-permeable cAMP analog, 8-bromo cAMP (10−7 M), and phorbol 12-myristate 13 acetate (10−7 M) potentiated HGF-induced MAPK phosphorylation. The effects of these analogs were antagonized by the protein kinase A (PKA) inhibitor H-89 (10−7 M) and the protein kinase C (PKC) inhibitor sphingosine (10−6 M), respectively. These results suggest that direct or indirect activation of both PKA and PKC represent a positive regulatory mechanism for stimulating MAPK induction by HGF.

【 授权许可】

Unknown