ENHANCEMENT OF DNA SYNTHESIS IN CULTURED ADULT RAT HEPATOCYTES BY 5-HT THROUGH STIMULATION OF 5-HT2 RECEPTOR

Hepatocytes were isolated from livers of adult male Sprague-Dawley rats and cultured in Williams'E Medium with 〔³ H〕 thymidine. The effect of 5-hydroxytryptamine (5-HT) was investigated through adding various concentrations (10^－8～10^－3 mol/L) of 5-HT to the hepatocyte cultures in the presence or absence of epidermal growth factor (EGF) and insulin. The involvement of 5-HT₂ receptor was examined by adding a 5-HT₂ receptor antagonist, ketanserin (10^－6 mol/L), to some of the cultures containing 5-HT. The increment of DNA synthesis was measured by 〔³ H〕 thymidine incorporation. The results showed that 5-HT₂ (≥10^－6 mol/L) significantly (P＜0.05) increased the amount of DNA synthesis induced by EGF and insulin in the cultured adult rat hepaptocytes. The effect of 5-HT in enhancing DNA synthesis began to appear at a concentration between 10^－7 and 10^－6 mol/L and reached maximum at concentrations of ≥10^－4 mol/L. The enhancement of DNA synthesis by 5-HT was significantly (P＜0.05) antagonized by ketanserin, suggesting that this effect of 5-HT was mediated by 5-HT₂ receptor subtype.