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J. Biochem, 1988, Vol. 103, No. 5 848-852
© 1988 Japanese Biochemical Society

research-article

Mechanism of Stimulation of DNA Synthesis Induced by Epinephrine in Primary Culture of Adult Rat Hepatocytes1

Shigeharu Takai*, Toshikazu Nakamura**, Nobuhiko Komi* and Akira Ichihara**,2

* The First Department of Surgery, School of Medicine, University of Tokushima Tokushima, Tokushima 770
** Institute for Enzyme Research, University of Tokushima Tokushima, Tokushima 770

2To whom correspondence should be addressed.

Addition of epinephrine to primary cultured adult rat hepatocytes stimulated their DNA synthesis dose-dependently, especially in presence of insulin and epidermal growth factor. This effect of epinephrine was strongly inhibited by an {alpha}1-antagonist, prazosin, but not by a ß-antagonist, propranolol, and was also slightly inhibited by an {alpha}2-antagonist, yohinbin. These results indicate that the stimulation of DNA synthesis of hepatocytes by epinephrine is mediated predominantly by an {alpha}1-action. 12-o-Tetradecanoylphorbol-13-acetate (TPA) or Ca2+-ionophore A-23187 stimulated DNA synthesis of Swiss 3T3 cells, but did not induce DNA synthesis of hepatocytes either singly or in combination. The fact that pretreatment of hepatocytes with TPA caused down-regulation of the stimulatory effect of epinephrine on DNA synthesis of hepatocytes within 15 min suggested that the effect of epinephrine on hepatocytes is mediated by its {alpha}1 receptor and that TPA activated protein kinase c in the hepatocytes. Addition of dibutyryl cGMP did not induce DNA synthesis of hepatocytes. Therefore, the {alpha}1-action of epinephrine that induce stimulation of DNA synthesis of primary cultured adult rat hepatocytes was apparently not mediated by either activation of phospholipid-dependent protein kinase or Ca2+ mobilization. Possible alternative mechanism was discussed.

1This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan.


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