BILIARY GLUTATHIONE AND SOME AMINO-ACIDS ARE MARKEDLY DIMINISHED WHENBILIARY PRESSURE IS ELEVATED

We studied the effects of a transient elevation in biliary pressure on biliary glutathione and amino acids in rats. Other biliary solutes mo nitored were total bile salt, P-i, which is a putative marker of parac ellular leakage, and glucose, which is reabsorbed from the biliary tra ct. Experiments were carried out on anesthetized rats intraduodenally infused with taurocholate to maintain bile flow during a 2-hr basal pe riod, a 4-hr pressure period during which the bile duct cannula was el evated until bile flow decreased to 1/3 the basal rate, and a 2-hr per iod after release of hydrostatic biliary pressure. We found that press ure treatment caused biliary concentrations of glutathione to progress ively decrease by 80%, while biliary P-i rapidly rose similar to 3- to 4-fold, bile salt gradually increased similar to 3-fold, and biliary glucose concentration progressively rose 15-fold. HPLC analysis of-mon obromobimane-derivatized biliary thiols indicated that the decline in biliary glutathione was not accompanied by an increase in its breakdow n products, cysteine and cysteinylglycine. Pressure treatment led to f our patterns of change in biliary amino acid concentrations: (1) incre ases of 29 to 76% for the basic amino acids lysine and arginine, which have very low bile/plasma ratios of about 0.1; (2) no change for the more water soluble amino acids with bile/plasma ratios close to 1.0, e .g., histidine and urea; (3) modest decreases of 16 to 48% for a varie ty of amino acids including serine, glutamate, and glycine; and (4) ma rked, progressive decreases of >50% for aromatic and branched chain am ino acids. By 2 hr after release of pressure, only the alterations in biliary glucose and some amino acids, particularly the branched chains , persisted. This is the first report of cholestasis-induced alteratio ns in biliary amino acids. (C) 1994 Academic Press, Inc.