Investigation of the role of ubiquinone in rat liver subcellular compartments

A major determinant of biliary lipid secretion is bile-salt secretion. Taurocholate (TC), a micelle-forming bile salt, was infused continuously at different rates in both isolated perfused livers and biliary-fistula rats. In both of these systems, infusion of TC brought about an elevated secretion of phosphatidylcholine for the duration of the TC infusion period. Initial phospholipid/bile-salt ratios in the bile were higher in the whole-animal model than in isolated livers, but at the higher infusion rates both secreted approx. 6 mol of phospholipid for every 100 mol of bile salt. The secretion of phospholipid, which was maintained even at high rates of bile-salt infusion, suggest a continuous and regulated phospholipid supply and secretion mechanism. In contrast, however, multiple short pulses of TC to the perfused liver, which brought about relatively equal biliary bile-salt output pulses, did not bring about equal phospholipid outputs, since the phospholipid peak size declined with each bile-salt pulse. These experiments taken together suggest either that a threshold (intracellular) bile-salt concentration may be required to 'switch-on' the phospholipid supply and that it may need to be maintained for continuous biliary phospholipid supply to the canalicular membrane.

Section: Origin Of the Biliary Lipidsmentioning

confidence: 99%

Control of biliary phospholipid secretion. Effect of continuous and discontinuous infusion of taurocholate on biliary phospholipid secretion

Rahman¹,

Hammond²,

Lowe³

et al. 1986

“…There have been several suggestions as to the origin of biliary lipid; these include material derived from an extracellular pool [(high-density lipoproteins) Casu et al (1981)], or from an intracellular pool (Yousef et al, 1975;Gregory et al, 1975;Kawamoto et al, 1980;Robins & Brunengraber, 1982). Transport of this intracellular lipid to the canaliculus membrane has been tentatively suggested to be via transport proteins (Coleman et al, 1977) (but for which direct evidence of involvement has to be found), or in some form of vesicle (Erlinger, 1981).…”

Section: Mechanisms Of Biliary Lipid Secretionmentioning

confidence: 99%

The effects of colchicine on secretion into bile of bile salts, phospholipids, cholesterol and plasma membrane enzymes: bile salts are secreted unaccompanied by phospholipids and cholesterol

Barnwell¹,

Lowe²,

Coleman³

1984

Colchicine, a drug which interferes with microtubular function, has no effect on the secretion of taurodehydrocholate into bile; it is therefore suggested that bile salts are unlikely to be packaged in vesicles during cellular transit from sinusoidal to canalicular membranes. Colchicine greatly reduces the secretion of phospholipid and cholesterol into bile; it is suggested that this is due to an interruption in the supply of vesicles bringing lipids to repair the canalicular membrane during bile salt output. In the absence of the protective effect of a continuous supply of repair vesicles, micelleforming bile salts damage the canalicular membrane; the increased concentration of plasma membrane enzymes in bile and the increased aspartate aminotransferase activity in plasma and bile are evidence of this damage. Damage to the canalicular membrane may also be an explanation for the reduction in taurocholate transport and the taurocholate-induced cholestasis which are seen with colchicine-treated livers. Such membrane damage is not observed in colchicine-treated livers during the secretion of the non-micelle forming bile salt, taurodehydrocholate.

“…At physiological rates of output the secretion of phospholipid and cholesterol into bile is dependent on the secretion of bile salts in an approximately linear relationship (Hoffman et al, 1975;Delage et al, 1976;Poupon et al, 1976;Sewell et al, 1979;Casu et al, 1981;Sama et al, 1982); this relationship is not seen, however, at very low or very high secretion rates of bile salts (Hardison & Apter, 1972). The characteristics of the bile-saltassociated lipid secretion are dependent on the physical properties of the bile salt.…”

mentioning

confidence: 99%

Rapid kinetic analysis of the bile-salt-dependent secretion of phospholipid, cholesterol and a plasma-membrane enzyme into bile

Lowe¹,

Barnwell²,

Coleman³

1984

Isolated rat livers were perfused under 'one-pass' conditions and bile was collected at 1 min intervals. After 1 min pulse, taurocholate appeared in the collected bile within 2 min, peak output occurring 2 min later. In contrast, the increased output of phospholipids and cholesterol was slower, peak output occurring 6-11 min after the original pulse of taurocholate. These results suggest that mixed micelles cannot be formed inside the cell or during passage of bile salts through the membrane, since bile salt and lipids should then parallel each other. The bile salts must therefore be pumped into the lumen and the lipids added subsequently, due to the actions of the bile salts in the canalicular lumen. It is suggested that the biliary lipid is obtained from microdomains of biliary-type lipid in the canaliculus membrane, which are vesiculated and solubilized by the action of bile salts. It is also suggested that this biliary-type lipid is brought continuously to the membrane via vesicle traffic; this traffic is increased during increased bile-salt output, and is a process that can be inhibited by colchicine.