Changes of the biliary canalicular membrane lipid content can affect membra
ne fluidity and biliary lipid secretion in rats. The immunosuppressant cycl
osporin A is known to cause intrahepatic cholestasis. This study investigat
ed whether cyclosporin A influenced canalicular membrane fluidity by alteri
ng membrane phospholipids or transporter expression. In male Sprague-Dawley
rats, a bile-duct cannula was inserted to collect bile, and sodium tauroch
olate was infused (100 nmol/min per 100 g) for 60 min. During steady-state
taurocholate infusion, cyclosporin A (20 mg/kg) or vehicle was injected int
ravenously and then bile was collected for 80 min. After killing the rats,
canalicular membrane vesicles were prepared. Expression of canalicular memb
rane transporters was assessed by Western blotting and canalicular membrane
vesicle fluidity was estimated by fluorescence polarization. Cyclosporin A
reduced biliary lipid secretion along with a disproportionate reduction of
lipids relative to bile acids. Cyclosporin A significantly decreased canal
icular membrane fluidity along with an increase of the cholesterol/phosphol
ipid molar ratio. Only expression of the transporter P-glycoprotein was inc
reased by cyclosporin A. Because canalicular membrane transporter expressio
n was largely unchanged by cyclosporin A despite a marked decrease of bilia
ry lipid secretion, transporter activity may partly depend upon canalicular
membrane fluidity.