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-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.
Sulaiman
Pyroja
P
Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, Kerala 682 022, India.
Joseph
Binoy
B
Kaimal
S Balarama
SB
Paulose
Cheramadathikudyil Skaria
CS
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D002273:Carcinogens; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D004052:Diethylnitrosamine; D004815:Epidermal Growth Factor / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
D002273:Carcinogens; D004273:DNA, Neoplasm; D017366:Serotonin Receptor Agonists; D053773:Transforming Growth Factor beta1; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D004052:Diethylnitrosamine; D004815:Epidermal Growth Factor; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin