Differential role of MAP kinases in stimulation of hepatocyte growth by EGF and G-protein-coupled receptor agonists.
Several agonists acting on G-protein-coupled receptors (GPCR) enhance the mitogenic effect of EGF in rat hepatocytes. Previous studies have shown that mitogen-activated protein (MAP) kinases are involved in the mitogenic effect of EGF. In the present study on cultured rat hepatocytes we show that although the comitogenic GPCR agonists prostaglandin F(2alpha), vasopressin, angiotensin II, and norepinephrine all activated ERK, blocking of the ERK pathway with the MEK inhibitor PD 98059 did not abolish their comitogenic effects. These GPCR agonists also activated p38, but the p38 blocker SB 203580 did not reduce the comitogenic effects. The mitogenic effect of EGF was inhibited completely by PD 98059 and partially by SB 203580. These results suggest that, in contrast to the mitogenic effect of EGF, the comitogenic effect of a group of GPCR agonists is independent of ERK and p38 in these cells.
Nilssen
Laila S
LS
Department of Pharmacology, University of Oslo, Oslo, N-0316, Norway. l.d.s.nilssen@labmed.uio.no
Hege Thoresen
G
G
Christoffersen
Thoralf
T
Sandnes
Dagny
D
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D015237:Dinoprost / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000819:agonists; D014667:Vasopressins / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D011956:Receptors, Cell Surface; D014667:Vasopressins; D000804:Angiotensin II; D004815:Epidermal Growth Factor; D004247:DNA; D015237:Dinoprost; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020962:Heterotrimeric GTP-Binding Proteins; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D009638:Norepinephrine