Decreased Hepatic 5-HT1A Receptors During Liver Regeneration and Neoplasia in Rats

In the present study we investigated the role of 5-hydroxytryptamine (5-HT) and 5-HT 1A receptor during liver regeneration after partial hepatectomy (PH) and N -nitrosodiethylamine (NDEA) induced hepatocellular carcinoma in male Wistar rats. 5-HT content was significantly increased during liver regeneration after PH and NDEA induced hepatocellular carcinoma. Scatchard analysis using 8-OH-DPAT, a 5-HT 1A specific agonist showed a decreased receptor during liver regeneration after PH and NDEA induced hepatocellular carcinoma . 5-HT when added alone to primary hepatocyte culture did not increase DNA synthesis but was able to increase the EGF mediated DNA synthesis and inhibit the TGFβ1 mediated DNA synthesis suppression in vitro. This confirmed the co-mitogenic activity of 5-HT. 8-OH-DPAT at a concentration of 10 −4 M inhibited the basal and EGF-mediated DNA synthesis in primary hepatocyte cultures. It also suppressed the TGFβ1-mediated DNA synthesis suppression. This clearly showed that activated 5-HT 1A receptor inhibited hepatocyte DNA synthesis. Our results suggest that decreased hepatic 5-HT 1A receptor function during hepatocyte regeneration and neoplasia has clinical significance in the control of cell proliferation.