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

2001 ◽  
Vol 354 (3) ◽  
pp. 591 ◽  
Author(s):  
Shigeyuki YASUMIBA ◽  
Susumu TAZUMA ◽  
Hidenori OCHI ◽  
Kazuaki CHAYAMA ◽  
Goro KAJIYAMA
Keyword(s):  
Cyclosporin A ◽  
Membrane Fluidity ◽  
Canalicular Membrane

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

2001 ◽  
Vol 354 (3) ◽  
pp. 591-596 ◽  
Author(s):  
Shigeyuki YASUMIBA ◽  
Susumu TAZUMA ◽  
Hidenori OCHI ◽  
Kazuaki CHAYAMA ◽  
Goro KAJIYAMA
Keyword(s):  
Cyclosporin A ◽  
Membrane Fluidity ◽  
Membrane Vesicle ◽  
Sodium Taurocholate ◽  
Molar Ratio ◽  
Biliary Lipid ◽  
Membrane Phospholipids ◽  
Lipid Secretion ◽  
Canalicular Membrane ◽  
Transporter Expression

Changes of the biliary canalicular membrane lipid content can affect membrane fluidity and biliary lipid secretion in rats. The immunosuppressant cyclosporin A is known to cause intrahepatic cholestasis. This study investigated whether cyclosporin A influenced canalicular membrane fluidity by altering membrane phospholipids or transporter expression. In male Sprague–Dawley rats, a bile-duct cannula was inserted to collect bile, and sodium taurocholate was infused (100nmol/min per 100g) for 60min. During steady-state taurocholate infusion, cyclosporin A (20mg/kg) or vehicle was injected intravenously and then bile was collected for 80min. After killing the rats, canalicular membrane vesicles were prepared. Expression of canalicular membrane 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 canalicular membrane fluidity along with an increase of the cholesterol/phospholipid molar ratio. Only expression of the transporter P-glycoprotein was increased by cyclosporin A. Because canalicular membrane transporter expression was largely unchanged by cyclosporin A despite a marked decrease of biliary lipid secretion, transporter activity may partly depend upon canalicular membrane fluidity.

Hepatocelluar cytoprotection by hydrophilic bile salts is through enhancing canalicular membrane fluidity and packing density

2000 ◽  
Vol 118 (4) ◽  
pp. A1422
Author(s):  
Yasumasa Asamoto ◽  
Susumu Tazuma ◽  
Hidenori Ochi ◽  
Tsuyoshi Kajihara ◽  
Hideyuki Hyougo ◽  
...  
Keyword(s):  
Membrane Fluidity ◽  
Packing Density ◽  
Bile Salts ◽  
Canalicular Membrane

Bile-salt hydrophobicity is a key factor regulating rat liver plasma-membrane communication: relation to bilayer structure, fluidity and transporter expression and function

2001 ◽  
Vol 359 (3) ◽  
pp. 605-610 ◽  
Author(s):  
Yasumasa ASAMOTO ◽  
Susumu TAZUMA ◽  
Hidenori OCHI ◽  
Kazuaki CHAYAMA ◽  
Hiroshi SUZUKI
Keyword(s):  
Body Weight ◽  
Plasma Membrane ◽  
Bile Salt ◽  
Membrane Fluidity ◽  
Bile Salts ◽  
Membrane Phospholipids ◽  
Canalicular Membrane ◽  
Liver Plasma Membrane ◽  
And Function ◽  
Transporter Expression

Bile-salt hydrophobicity regulates biliary phospholipid secretion and subselection. The aim of this study was to determine whether bile salts can influence liver plasma membrane phospholipids and fluidity in relation to the ATP-dependent transporter. Rats were depleted of bile salts by overnight biliary diversion and then sodium taurocholate was infused intravenously at a constant rate (200nmol/min per 100g of body weight), followed by infusion of bile salts with various hydrophobicities (taurochenodeoxycholate, tauroursodeoxycholate, tauro-β-muricholate, tauro-α-muricholate at 200nmol/min per 100g of body weight). The hydrophobicity of the infused bile salts correlated with that of biliary phospholipids, but was inversely related to that of the canalicular membrane bilayer. Canalicular membrane fluidity (estimated by 1,6-diphenyl-1,3,5-hexatriene fluorescence depolarization) and expression of multidrug-resistance proteins (Mrp2, Mrp3) and apical Na+-dependent bile-salt transporter (ASBT) were increased by hydrophilic bile salts, although there was no marked change in the expression of P-glycoprotein subfamilies (Mdr2). Bile-salt export pump (Bsep) expression was increased along with increasing bile-salt hydrophobicity. Bile salts modulate canalicular membrane phospholipids and membrane fluidity, as well as the ATP-dependent transporter expression and function, and these actions are associated with their hydrophobicity. The cytoprotective effect of hydrophilic bile salts seems to be associated with induction of Mrp2, Mrp3 and ASBT.

Sign in / Sign up

Export Citation Format

Share Document