Hepatic organic anion uptake in the rat.

Abstract

A B S T R A CT(a) hepatic uptake determined by direct tissue measurement could be accurately estimated from the plasma disappearance data; (b) saturation of hepatic uptake with increasing dose was readily demonstrated for each of these three organic anions, and in each instance a plot of V versus dose took the form of a rectangular hyperbola analyzable in terms of Michaelis-Menten kinetics; (c) for BR, the saturable uptake process showed a V.a. more than 100 times the normal net transfer rate from plasma to bile; (d) hepatic uptake of BR, BSP, and ICG showed relatively selective, mutually competitive inhibition; glycocholic acid did not inhibit hepatic uptake of any of these substances; and (e) "countertransport" could be demonstrated for each of the three test substances. These data are compatible with the existence of a carrier-mediated transport process for hepatic uptake of each of these three organic anions and clarify the relationship of hepatic BR uptake to its overall transport from plasma to bile.

Pharmacokinetics and biliary excretion of bromosulphophthalein, [3H]‐ouabain and [3H]‐taurocholic acid in rats with glycerol‐induced acute renal failure

“…These changes in the way in which the liver handles BSP are qualitatively similar to those found previously with ICG (Bowmer et al, 1982a;Yates etal., 1983a,b,c). This is not surprising because there is evidence to suggest that both dyes share the same pathway for hepatic uptake (Scharschmidt et al, 1975;Schwenk et al, 1976).…”

“…Evidence for this comes largely from studies of competition for transport between pairs of substances. These studies have revealed a number of different routes for organic anions (Alpert et al, 1969;Scharschmidt et al, 1975;Schwenk et al, 1976), cations (Solomon & Schanker, 1963) and uncharged molecules (Kupferberg & Schanker, 1968;Klassen, 1978).…”

Oatp1a1 Requires PDZK1 to Traffic to the Plasma Membrane by Selective Recruitment of Microtubule-Based Motor Proteins

“…The hepatocyte serves as a major site of organic anion clearance from the circulation (Scharschmidt et al, 1975;Wolkoff, 2012). Many of these compounds are poorly soluble in aqueous solution, and circulate bound to proteins such as albumin (Wolkoff et al, 1987;Choi et al, 2009).…”

Organic Anion Transporting Polypeptides

“…Zhang, Strong, Qiu, Lesko, & Huang, 2006;. OATPs were identified on their basis to transport BSP, a substrate which was thought to be transported (in part) by a postulated bilirubin transport system (Clarenburg & Kao, 1973;Scharschmidt, et al, 1975). Many years after their identification it was indeed demonstrated that hOATP1B1 and hOATP1B3 could mediate bilirubin transport (Briz, Serrano, MacIas, Gonzalez-Gallego, & Marin, 2003;Cui, Konig, Leier, Buchholz, & Keppler, 2001).…”