Cyclosporin A reduces canalicular membrane fluidity and regulates transporter function in rats

Citation
S. Yasumiba et al., Cyclosporin A reduces canalicular membrane fluidity and regulates transporter function in rats, BIOCHEM J, 354, 2001, pp. 591-596
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL JOURNAL
ISSN journal
0264-6021 → ACNP
Volume
354
Year of publication
2001
Part
3
Pages
591 - 596
Database
ISI
SICI code
0264-6021(20010315)354:<591:CARCMF>2.0.ZU;2-C
Abstract
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.