Decreased hepatic 5-HT1A receptors during liver regeneration and neoplasia in rats

作者：Sulaiman Pyroja; Joseph Binoy; Kaimal S Balarama; Paulose Cheramadathikudyil Skaria^*

来源：Neurochemical Research, 2008, 33(3): 444-449.

DOI：10.1007/s11064-007-9452-4

• 5-HT
• 5-HT1A
• receptor
• N-nitrosodiethylamine
• partial hepatectomy
• 8-OH-DPAT
• hepatic neoplasia

In the present study we investigated the role of 5-hydroxytryptamine (5-HT) and 5-HT1A 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-HT1A 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 TGF beta 1 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 TGF beta 1-mediated DNA synthesis suppression. This clearly showed that activated 5-HT1A receptor inhibited hepatocyte DNA synthesis. Our results suggest that decreased hepatic 5-HT1A receptor function during hepatocyte regeneration and neoplasia has clinical significance in the control of cell proliferation.

• 出版日期2008-3