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Effect of 5-HT7 Receptor Blockade on Liver Regeneration After 60-70% Partial Hepatectomy

Effect of 5-HT7 Receptor Blockade on Liver Regeneration After 60-70% Partial Hepatectomy

Konstantinos N Tzirogiannis, Kalliopi T Kourentzi, Sofia Zyga, Vassiliki Papalimneou, Maria Tsironi, Agni D Grypioti, Ioannis Protopsaltis, Dimitrios Panidis, Georgios I Panoutsopoulos

BMC Gastroenterol. 2014 Nov 30;14:201.

PMID: 25433672

Abstract:

Background:
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. The aim of the present study was to investigate the effect of 5-HT7 receptor blockade on liver regeneration after partial hepatectomy.
Methods:
Male 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 [(3)H]-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.
Results:
Liver regeneration peaked at 24 h ([(3)H]-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 ([(3)H]-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.
Conclusions:
In conclusion, 5-HT7 receptor is a novel type of serotonin receptor implicated in hepatocyte proliferation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP261901579	SB-269970 hydrochloride		261901-57-9	Price

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