Biliary secretion of organic anions in the dog: association with defined lipid particles

Abstract

Organic anions have recently been found to partition in vitro into various biliary lipid particulate species according to their relative hydrophobicities. To establish the physiological relevance of these observations, we intravenously injected various radiolabeled organic anions and assessed the distributions of parent compounds and their metabolites to lipid particles in canine bile. Partitioning into various biliary lipid particles was determined by gel permeation chromatography. Relative hydrophobicities of the various organic anions and their radiolabeled conjugates were determined by reverse-phase high-pressure liquid chromatography. A strong positive correlation (P less than 0.001) was found between percent vesicular association and degree of hydrophobicity for a given organic anion and/or its more polar conjugate. We conclude that 1) the hydrophobic-hydrophilic balance of organic anions is a key factor governing their partitioning to lipid particles secreted in bile; 2) the present study agrees well with our previously published in vitro observations; and 3) other chemical constituents, e.g., proteins, mucin, etc., appear to have little or no effect on organic anion transport in bile.

Hepatic Elimination of Indocyanine Green with Special Reference to Distribution Kinetics and the Influence of Plasma Protein Binding

“…It is an indicator and a weak acid with pKA 3.27 (Bjornsson et al 1982). It is highly hydrophobic and lipophilic, even compared to other cholephilic anions (Tazuma et al 1988), and this may be the reason why ICG does not pass dialysis membranes (Baker 1966;Gentile et al 1985). ICG is green with an absorption maximum of 780 nM in distilled water and methanol, 800 nm in an albumin containing solution, and 805 nm in plasma (Sutterer et al 1966;Gathje et al 1970;Tripp et al 1973;Valerie 1973;Gentile et al 1985).…”

“…The above studies suggest that MRP2kMOAT is not the only pathway for ICG excretion into bile. Exocytosis may be an alternative pathway because ICG excretion is inhibited by colchicin (Mori et al 1987) and the more hydrophobic organic anions, such as ICG and rose bengal, are primarily found in vesicles in the bile (Tazuma et al 1988).…”

New insights into the mechanism of bile acid—induced biliary lipid secretion

“…"~,~'~ We collected biles from control rats shortly after injection of the various organic anions and immediately performed gel filtration chromatography using a Sepharose CL-4B co1umn.118,119,128 The capacity of an organic anion to inhibit biliary lipid secretion in vivo was found to coincide with its preferential association with biliary bile acid micelles during gel filtration chromatography. Conversely, organic anions that did not interfere with biliary lipid secretion in vivo showed a high affinity for biliary phospholipid and cholesterol vesicles.lZ8 Based on data from the literature4".53-",64,~5, 118,119 as well as on our own observation^,^^^^^^,^^^ it . was concluded that only relatively hydrophilic organic anions have the capacity to uncouple biliary lipid from bile acid secretion, presumably by means of a physico-chemical interaction with bile acids inside the bile canaliculus (Fig.…”

Transport of organic anions in the liver. An update on bile acid, fatty acid, monocarboxylate, anionic amino acid, cholephilic organic anion, and anionic drug transport

“…In a recent comparative study, the influence of substrate hydrophobicity on the biliary elimination of tracer doses of phenol red, BSP and rose bengal was investigated in the isolated perfilsed rat liver in situ (Tazuma et al 1988;Tokumo et al 1991;Aoyama et al 1991). The fastest elimination was associated with the most hydrophilic compound, phenol red; the most prolonged elimination was associated with the most hydrophobic compound, rose bengal; BSP was in between.…”