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Hepatocyte growth factor induces calcium mobilization and inositol phosphate production in rat hepatocytes
Author(s) -
Baffy György,
Yang Lijun,
Michalopoulos George K.,
Williamson John R.
Publication year - 1992
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041530213
Subject(s) - inositol , mobilization , hepatocyte , calcium , microbiology and biotechnology , hepatocyte growth factor , inositol phosphate , chemistry , phosphate , growth factor , biochemistry , biology , in vitro , receptor , archaeology , organic chemistry , history
The effects of hepatocyte growth factor (HGF) on intracellular Ca 2+ mobilization were studied using fura‐2‐loaded single rat hepatocytes. Hepatocytes microperfused with different amounts of HGF responded with a rapid concentration‐dependent rise in the cytosolic free Ca 2+ concentration with a maximum increase of 142% at 80 ng/ml of HGF. The lag period of the Ca 2+ response was decreased with increasing HGF concentrations, being 64 ± 12 s, 42 ± 6 s, and 14 ± 2 s, respectively, with 8, 20, and 80 ng/ml of HGF. The detailed pattern of Ca 2+ transients, however, was variable. Out of 16 cells tested using 20 ng/ml of HGF, 68% showed sustained oscillatory responses, whereas other cells showed a sustained increase in the cytosolic‐free Ca 2+ upon exposure to HGF, which was dependent on the presence of extracellular Ca 2+ . HGF also induced Ca 2+ entry across the plasma membrane. Mobilization of Ca 2+ by HGF was accompanied by a rapid accumulation of inositol 1,4,5‐trisphosphate (Ins 1,4,5‐P 3 ). The effects of HGF and epidermal growth factor (EGF) were comparable and partly additive for Ins 1,4,5‐P 3 production and for the sustained phase of Ca 2+ mobilization. Preincubation of cells with 10 μM of genistein to inhibit protein tyrosine kinases abolished the HGF‐induced Ca 2+ response and also inhibited HGF‐induced Ins 1,4,5‐P 3 production in rat liver cells. These data indicate that early events in the signal transduction pathways mediated by HGF and EGF have in common the requirements for tyrosine kinase activity, Ins 1,4,5‐P 3 production, and Ca 2+ mobilization. © 1992 Wiley‐Liss, Inc.