Modifying hepatic phospholipid synthesis associates with biliary phospholipid secretion rate in a transporter-independent manner in rats - Relation to canalicular membrane fluidity

Biliary phospholipid secretion is mediated by a multidrug resistance gene p roduct, and its molecular subselection occurs at the site of secretion to m odulates bile metastability. The aim of this study was to determine the eff ect of modifying hepatic phospholipid synthesis on canalicular phospholipid transporter expression and membrane fluidity, Bile-duct cannulation was pe rformed in male Sprague-Dawley rats pretreated with or without intravenous infusion of dimethylethanolamine, an intermediate phospholipid metabolite a long the pathway of phosphatidylcholine synthesis of phosphatidylethanolami ne N-methylation (0.01 mg/min/100 g body wt) for 15 hr, followed by sodium taurocholate infusion (50 nmol/min/100 g body wt) with or without sulfobrom ophthalein (50 nmol/min/100 g body wt), Dimethylethanolamine enhanced bilia ry phospholipid secretion in association with a decrease in biliary phospho lipid hydrophobicity. Dimethylethanolamine also increased canalicular membr ane fluidity defined by 1,6-diphenyl-1,3,5-hexatriene fluorescence depolari zation, whereas the expression of multidrug resistance gene product and mul tidrug resistance associated protein was unchanged. In contrast, a dispropo rtionote reduction of biliary phospholipid secretion caused by sulfobromoph thalein (uncoupling) was enhanced by under the treatment with dimethylethan olamine. In conclusion, the increase in biliary phospholipid secretion and canalicular membrane fluidity without a drastic change of its canalicular t ransporter by dimethylethanolamine suggests that such a canalicular membran e fluidity facilitates the transporter activity and/or phospholipid molecul ar movement from the canalicular outer membrane into the bile. A more drast ic reduction in phospholipid secretion under sulfobromophthalein-caused unc oupling indicates the possibility of a preferential distribution of relativ ely hydrophilic phosphatidylcholine molecules to bile salt micelles since s ulfobromophthalein is known to reduce the micellar capacity to extract memb rana lipids fur biliary secretion.