Abstract
BackgroundSerotonin exhibits a vast repertoire of actions including cell proliferation and differentiation. The effect of serotonin, as an incomplete mitogen, on liver regeneration has recently been unveiled and is mediated through 5-HT2 receptor. The aim of the present study was to investigate the effect of 5-HT7 receptor blockade on liver regeneration after partial hepatectomy.MethodsMale Wistar rats were subjected to 60-70% partial hepatectomy. 5-HT7 receptor blockade was applied by intraperitoneal administration of SB-269970 hydrochloride two hours prior to and sixteen hours after partial hepatectomy and by intraperitoneal administration of SB-258719 sixteen hours after partial hepatectomy. Animals were sacrificed at different time points until 72 h after partial hepatectomy. Liver regeneration was evaluated by [3H]-thymidine incorporation into hepatic DNA, the mitotic index in hematoxylin-eosin (HE) sections and by immunochemical detection of Ki67 nuclear antigen. Reversion of 5-HT7 blockade was performed by intraperitoneal administration of AS-19. Serum and liver tissue lipids were also quantified.ResultsLiver regeneration peaked at 24 h ([3H]-thymidine incorporation into hepatic DNA and mitotic index by immunochemical detection of Ki67) and at 32 h (mitotic index in HE sections) in the control group of rats. 5-HT7 receptor blockade had no effect on liver regeneration when applied 2 h prior to partial hepatectomy. Liver regeneration was greatly attenuated when blockade of 5-HT7 receptor was applied (by SB-258719 and SB-269970) at 16 h after partial hepatectomy and peaked at 32 h ([3H]-thymidine incorporation into hepatic DNA and mitotic index by immunochemical detection of Ki67) and 40 h (mitotic index in HE sections) after partial hepatectomy. AS-19 administration totally reversed the observed attenuation of liver regeneration.ConclusionsIn conclusion, 5-HT7 receptor is a novel type of serotonin receptor implicated in hepatocyte proliferation.
Highlights
Serotonin exhibits a vast repertoire of actions including cell proliferation and differentiation
All surgical procedures were performed between 07.0009.00 am with the animals under light ether anesthesia. 5-HT7 receptor blockade was applied by intraperitoneal administration of SB-269970 hydrochloride (Sigma-Aldrich) and SB-258719 (Tokris Bioscience, Ellisville Missouri, USA)
In rats subjected to 60-70% partial hepatectomy, liver regeneration as evaluated by [3H]-thymidine incorporation into hepatic DNA, peaked at 24 and 32 h after partial hepatectomy and high rates were observed at 40 h
Summary
Serotonin exhibits a vast repertoire of actions including cell proliferation and differentiation. The effect of serotonin, as an incomplete mitogen, on liver regeneration has recently been unveiled and is mediated through 5-HT2 receptor. A number of recent in vivo studies including studies from our laboratory have elucidated the role of serotonin in liver regeneration after partial hepatectomy [7,8,9] with platelets to be the major reservoir accounting for the increased hepatic concentrations of the monoamine during liver regeneration. From experiments with 5-HT2 receptor blockade with ketanserin or ritanserin in our laboratory, it has become evident that serotonin exerts its actions mainly at the G1/S transition point and this suggests implication of the monoamine in the control of this major restrictive checkpoint of the cell cycle [8]. In in vitro experiments, serotonin induces dose-dependent increase in DNA synthesis only in the presence of insulin and epidermal growth factor (EGF) [7] and recently serotonin has been shown to promote hepatocellular cancer growth in human hepatocellular cancer cell lines [10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
