Effects of 5-hydroxytamine and its antagonists on hepatic stellate cells.
BACKGROUND
Hepatic stellate cell (HSC) plays a key role in hepatic fibrosis. This study was undertaken to investigate the expression of 5-hydroxytamine receptors in HSC and the effect of 5-hydroxytamine on biological characteristics of HSC.


METHODS
Liver ex vivo perfusion of collagenase and density gradient centrifugation were used to isolate HSCs. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the expression of 5-hydroxytamine receptor subtypes 1A, 2A, 2B and 3. Western blot hybridization was used to elucidate the effect of 5-hydroxytamine and its 2A receptor antagonist ketanserin and 3 receptor antagonist ondanosetron on the expression of transforming growth factor-beta1 (TGF-beta1) and Smad4 in HSC.


RESULTS
HSC expressed 5-hydroxytamine receptor subtypes 1A, 2A and 2B. 5-hydroxytamine significantly increased the expression of TGF-beta1 and Smad4 in HSC (P<0.05). This action can be antagonized by ketanserin, not by ondanosetron.


CONCLUSIONS
HSC expresses 5-hydroxytamine receptors. 5-Hydroxytamine could effect the biological characteristics of HSC through its receptor mediation, and may play a role in the pathogenesis of liver cirrhosis and portal hypertension.
Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China.
Tao
T
Li
Shan-Geng
SG
Weng
Xi-Sheng
XS
Leng
Ji-Run
JR
Peng
Yu-Hua
YH
Wei
Dong-Cheng
DC
Mou
Wan-Xiang
WX
Wang
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D007650:Ketanserin / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000209:etiology; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D012313:RNA / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D051901:Smad4 Protein / Q000096:biosynthesis / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000187:drug effects; D053773:Transforming Growth Factor beta1
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D051901:Smad4 Protein; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D012701:Serotonin; D017294:Ondansetron; D012313:RNA; D007650:Ketanserin