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

Abstract

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 (200 nmol/min per 100 g of body weight), followed by infusion of bile salts with various hydrophobicities (taurochenodeoxycholate, tauroursodeoxycholate, tauro-beta-muricholate, tauro-alpha-muricholate at 200 nmol/min per 100 g 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.