title: Effect of 5-HT7 receptor blockade on liver regeneration after 60-70% partial hepatectomy.
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.
authors.affiliation: Department of Experimental Pharmacology, Medical School, Athens University, Athens, 11527, Greece. tziro@hol.gr.
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Tzirogiannis
authors.affiliation: Department of Experimental Pharmacology, Medical School, Athens University, Athens, 11527, Greece. kthk@otenet.gr.
authors.forename: Kalliopi T
authors.initials: KT
authors.lastname: Kourentzi
authors.affiliation: Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, Sparta, 23100, Greece. zygas@spa.forthnet.gr.
authors.forename: Sofia
authors.initials: S
authors.lastname: Zyga
authors.affiliation: Department of Internal Medicine, Elpis General Hospital, Athens, 11522, Greece. vplimneou@yahoo.gr.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Papalimneou
authors.affiliation: Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, Sparta, 23100, Greece. tsironi@uop.gr.
authors.forename: Maria
authors.initials: M
authors.lastname: Tsironi
authors.affiliation: Department of Experimental Pharmacology, Medical School, Athens University, Athens, 11527, Greece. agrypiot@med.uoa.gr.
authors.forename: Agni D
authors.initials: AD
authors.lastname: Grypioti
authors.affiliation: Department of Internal Medicine, Tzanio General Hospital of Piraeus, Piraeus, 18537, Greece. ioprot@gmail.com.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Protopsaltis
authors.affiliation: Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, Sparta, 23100, Greece. dpan72@gmail.com.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Panidis
authors.affiliation: Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, Orthias Artemidos and Plateon, Sparta, 23100, Greece. gpanouts@uop.gr.
authors.forename: Georgios I
authors.initials: GI
authors.lastname: Panoutsopoulos
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008115:Liver Regeneration; D008297:Male; D010636:Phenols / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D000096926:Benzenesulfonamides
chemical_list: D004247:DNA; D008055:Lipids; D010636:Phenols; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; D013936:Thymidine; C111309:3,N-dimethyl-N-(1-methyl-3-(4-methylpiperidin-1-yl)propyl)benzenesulfonamide; D000096926:Benzenesulfonamides; C404922:SB 269970; C104425:serotonin 7 receptor