Taurolithocholate impairs bile canalicular motility and canalicular bile secretion in isolated rat hepatocyte couplets.
OBJECTIVE
To investigate the effects of taurolithocholate (TLC) on the canalicular motility in isolated rat hepatocyte couplets (IRHC).


METHODS
TLC was added to IRHC at concentrations of 10 and 50 mumol/L, respectively. In each group, five time-lapse movies containing 3 representative bile canaliculi were taken under phase-contrast microscopy for 12 h. The number of bile canalicular contractions and the intervals between consecutive canalicular contractions were calculated. Furthermore, the effects of TLC on IRHC were examined by transmission electron microscopy.


RESULTS
The bile canalicular contractions were spontaneous and forceful in the controls. Active vesicular movement was observed in the pericanalicular region. Immediately after the addition of TLC, the bile canaliculi were deformed, and canalicular bile was incorporated into the vacuoles. The canaliculi were gradually dilated, and canalicular contractions were markedly inhibited by TLC. The vesicular movements became extremely slow in the pericanalicular region. The number of canalicular contractions significantly decreased in the TLC-treated groups, as compared with that in the controls. The time intervals were prolonged, as the TLC dosage increased, indicating that bile secretion into the canaliculi was impaired with TLC. Transmission electron microscopy revealed the lamellar transformation of the canalicular membranes in IRHC treated with TLC.


CONCLUSIONS
TLC impairs both the bile canalicular contractions and the canalicular bile secretion, possibly by acting directly on the canalicular membranes in TLC-induced cholestasis.
Watanabe
Norihito
N
Division of Gastroenterology, Department of Internal Medicine, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan. norihito@is.icc.u-tokai.ac.jp
Kagawa
Tatehiro
T
Kojima
Seiichiro
S
Takashimizu
Shinji
S
Nagata
Naruhiko
N
Nishizaki
Yasuhiro
Y
Mine
Tetsuya
T
D000818:Animals; D001648:Bile Canaliculi / Q000166:cytology* / Q000378:metabolism; D001652:Bile Ducts / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D002779:Cholestasis; D004305:Dose-Response Relationship, Drug; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar; D013658:Taurolithocholic Acid / Q000494:pharmacology*; D013997:Time Factors
D002756:Cholagogues and Choleretics; D013658:Taurolithocholic Acid