INDUCTION OF DNA-SYNTHESIS IN PRIMARY CULTURES OF RAT HEPATOCYTES BY SEROTONIN - POSSIBLE INVOLVEMENT OF SEROTONIN S-2 RECEPTOR

Citation
S. Balasubramanian et Cs. Paulose, INDUCTION OF DNA-SYNTHESIS IN PRIMARY CULTURES OF RAT HEPATOCYTES BY SEROTONIN - POSSIBLE INVOLVEMENT OF SEROTONIN S-2 RECEPTOR, Hepatology, 27(1), 1998, pp. 62-66
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Gastroenterology & Hepatology
Journal title
ISSN journal
0270-9139
Volume
27
Issue
1
Year of publication
1998
Pages
62 - 66
Database
ISI
SICI code
0270-9139(1998)27:1<62:IODIPC>2.0.ZU;2-K
Abstract
The involvement of serotonin and its receptor subtype in the induction of hepatocyte DNA synthesis was investigated in primary cultures of a dult rat hepatocytes. Serotonin caused a dose-dependent increase in DN A synthesis in primary cultures of rat hepatocytes in the presence of epidermal growth factor (EGF) and insulin, as measured by [H-3]thymidi ne incorporation. The serotonin S-2 receptor antagonists, ketanserin ( 10(-6) mol/L) and spiperone (10(-6) mol/L), blocked stimulation of DNA synthesis by serotonin. Displacement studies on [H-3]5-hydroxytryptam ine (5-HT) binding to crude membranes from control and regenerating li ver tissue, using cold ketanserin and spiperone, showed an increased i nvolvement of S-2 receptors of serotonin in the regenerating liver dur ing the DNA-synthetic phase. Serotonin enhanced the phosphorylation of a 40-kd substrate protein of protein kinase C (PKC) in the regenerati ng liver during the DNA synthetic phase of the hepatocyte cell cycle. This was blocked by ketanserin, indicating that serotonin S-2 receptor activates PKC, an important second messenger in cell growth and divis ion, during rat liver regeneration. Our results show that serotonin ca n act as a potent hepatocyte comitogen and induce DNA synthesis in pri mary cultures of rat hepatocytes, which is suggested to be mediated th rough the serotonin S-2 receptors of hepatocytes.