Induction of choleresis by immunosuppressant FK506 through stimulation of insulin-like growth factor-I production in the liver of rats.
FK506 (Tacrolimus) is an effective immunosuppressant currently used worldwide in organ transplantation. Based on our recent findings that insulin-like growth factor-I (IGF-I) is important for the stimulation of choleresis in vivo, in this study we investigated the effect of FK506 on bile flow and the plasma and hepatic levels of IGF-I in rats. Intravenous treatment of rats with FK506 resulted in a significant increase in bile flow, whereas cyclosporin A induced a significant decrease. A significant increase in plasma levels of IGF-I was observed in rats 30 min after a single intravenous administration of FK506. Oral treatment of rats with FK506 for 1 week also resulted in an increase in both plasma and hepatic levels of IGF-I. Overall, this study showed that FK506 treatment increased bile flow and also induced an increase in the plasma and hepatic levels of IGF-I in rats, suggesting that a stimulation of hepatic IGF-I production by FK506 may contribute to its choleretic profile.
Kawamura
I
I
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 2-1-6, Kashima, Yodogawa-ku, 532-8514, Osaka, Japan. ikuo_kawamura@po.fujisawa.co.jp
Takeshita
S
S
Fushimi
M
M
Mabuchi
M
M
Seki
J
J
Goto
T
T
D000818:Animals; D001646:Bile / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D007016:Hypophysectomy; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D007334:Insulin-Like Growth Factor I; D016572:Cyclosporine; D016559:Tacrolimus