Effect of serotonin receptor 2 blockage on liver regeneration after partial hepatectomy in the rat liver.
The effect of serotonin receptor 2 blockade (5-HT(2)) on liver regeneration after 30-34% and 60-70% partial hepatectomy in the rat liver was investigated.


METHODS
Male Wistar rats were subjected to 60-70% (group I) and 30-34% (group II) partial hepatectomy. Serotonin receptor 2 blockade was exerted by intraperitoneal administration of ketanserin at different doses and time points after partial hepatectomy. The rats of all groups were killed at different time points until 96 h after partial hepatectomy. The rate of liver regeneration was evaluated by the mitotic index in hematoxylin and eosin sections, the immunochemical detection of Ki67 and proliferating cell nuclear antigens, the rate of [(3)H]-thymidine incorporation into hepatic DNA and liver thymidine kinase enzymatic activity.


RESULTS
Liver regeneration peaked at 24 and 32 h after partial hepatectomy in 60-70% hepatectomized rats. In 30-34% hepatectomized rats liver regeneration peaked at 60 h, whereas low rates of regenerative activity were observed between 24 and 72 h after partial hepatectomy. Ketanserin administration arrested liver regeneration only when administered at 16 h after 60-70% partial hepatectomy. Ketanserin also abrogated the observed peak of regenerative activity at 60 h in 30-34% hepatectomized rats when administered at 52 h after partial hepatectomy. All indices of liver regeneration were affected by ketanserin administration.


CONCLUSIONS
Serotonin receptor 2 blockade can arrest liver regeneration only when administered close to G1/S transition point, and that while serotonin may be a cofactor for DNA synthesis, it does not play a role in initiation of liver regeneration.
Department of Experimental Pharmacology, Medical School, Athens University, Athens, Greece.
George K
GK
Papadimas
Konstantinos N
KN
Tzirogiannis
Georgios I
GI
Panoutsopoulos
Maria D
MD
Demonakou
Spyridon D
SD
Skaltsas
Rosa I
RI
Hereti
Zeta
Z
Papadopoulou-Daifoti
Michael G
MG
Mykoniatis
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006498:Hepatectomy / Q000379:methods*; D007650:Ketanserin / Q000008:administration & dosage / Q000494:pharmacology*; D019394:Ki-67 Antigen / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008940:Mitotic Index; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D013937:Thymidine Kinase / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D044348:Receptors, Serotonin, 5-HT2; D012702:Serotonin Antagonists; D004247:DNA; D007650:Ketanserin; D013937:Thymidine Kinase