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

Bile-salt hydrophobicity regulates biliary phospholipid secretion and subse lection. The aim of this study was to determine whether bile salts can infl uence liver plasma membrane phospholipids and fluidity in relation to the A TP-dependent transporter. Rats were depleted of bile salts by overnight bil iary 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 (taurochenodeoxy-cholate, taur oursodeoxycholate, 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 rel ated to that of the canalicular membrane bilayer. Canalicular membrane flui dity (estimated by 1,6-diphenyl-1,3,5-hexatriene fluorescence depolarizatio n) and expression of multidrug-resistance proteins (Mrp2, Mrp3) and apical Na+-dependent bile-salt transporter (ASBT) were increased by hydrophilic bi le salts, although there was no marked change in the expression of P-glycop rotein subfamilies (Mdr2). Bile-salt export pump (Bsep) expression was incr eased along with increasing bile-salt hydrophobicity. Bile salts modulate c analicular membrane phospholipids and membrane fluidity, as well as the ATP -dependent transporter expression and function, and these actions are assoc iated with their hydrophobicity. The cytoprotective effect of hydrophilic b ile salts seems to be associated with induction of Mrp2, Mrp3 and ASBT.