Taurocholate transport by rat intestinal basolateral membrane vesicles. Evidence for the presence of an anion exchange transport system.

Abstract

The transport of bile acid was studied in basolateral membrane vesicles isolated from rat small intestine. Taurocholate transport into an osmotically reactive intravesicular space was Na+ independent. The uptake of taurocholate in jejunal and ileal vesicles preloaded with sulfate was stimulated with respect to uptake in unpreloaded vesicles. Glycocholate inhibited the transstimulation of taurocholate uptake by sulfate. Sulfate and taurocholate uptake in ileal vesicles preloaded with bicarbonate was stimulated with respect to uptake in unpreloaded vesicles. Taurocholate inhibited the transstimulation of sulfate uptake by bicarbonate.When ileal vesicles were loaded withp-aminohippurate, an early transstimulation of taurocholate was found that exceeded equilibrium uptake, was insensitive to a K+ diffusion potential, and was cis-inhibited by taurocholate, glycocholate, pyruvate, paminohippurate, probenecid, chloride, sulfate, and bicarbonate. These data indicate the presence of an anion exchanger in intestinal basolateral membrane vesicles that may be involved in the exit of bile acids from the enterocyte.

Studies on Intestinal Absorption of Sulpiride. (1): Carrier-Mediated Uptake of Sulpiride in the Human Intestinal Cell Line Caco-2.

“…30) In the present study, however, no significant stimulation was observed by preloading with organic cation transporter OCT3 substrate, guanidine, 31) or organic anion transporter MCT1 and/or AE2 substrates, nicotinic acid 32,33) and p-aminohippuric acid. 34,35) PGlycoprotein, and organic cation transporter OCTN1 and OCTN2 substrates, quinidine 36) and verapamil 36) also had no significant effect. We speculated that this was because of the simultaneous inhibition of sulpiride uptake and efflux by these compounds.…”

The Heteromeric Organic Solute Transporter α-β, Ostα-Ostβ, Is an Ileal Basolateral Bile Acid Transporter

“…However, is the fact that Ost␣-Ost␤ mediates taurocholate uptake and is still consistent with its postulated role in basolateral efflux. Previous studies have demonstrated bi-directional bile acid transport using ileal basolateral membranes (4). By functioning as a facilitative transporter or an anion exchanger, Ost␣-Ost␤ is predicted to move bile acids down their electrochemical gradient either into or out of the cell.…”

“…Using rat ileal basolateral membrane vesicles, bile acid transport was trans-stimulated by sulfate, bicarbonate ions, and p-aminohippurate, suggesting a sodium-independent anion exchange mechanism (4). Subsequent affinity labeling using tritiated bile acid photoprobes and subcellular fractionation studies implicated a 54-kDa protein enriched in the basolateral membrane (5-7); however no specific transporter was identified.…”

“…The majority of bile acids are reabsorbed from the intestine, returned to the liver via the portal venous circulation, and resecreted into bile (1). The major mechanism for intestinal absorption is active transport by the well characterized ileal apical sodium bile acid co-transporter (ASBT, 1 gene name Slc10a2) (3,4) in the distal ileum. Loss-of-function mutations in the human ASBT gene are associated with intestinal bile acid malabsorption (2), and targeted deletion of the ASBT gene eliminates enterohepatic cycling of bile acids in mice (3).…”

Inhibition of ileal bile acid transport by cyclosporin A in rat

“…Therefore, in spite of inhibition of intestinal bile acid absorption serum bile acid levels may be increased during treatment due to their decreased biliary secretion. Active bile acid absorption by the ileal enterocyte involves at least two carrier systems, a sodiumcoupled cotransport [ 16-181, which recently has been cloned and characterized [ 191 and an anion-exchange system [18,20]. Our data indicate an inhibitory effect of CsA on intestinal transport of bile acids in ileum of rat and at present it is unclear which intestinal transport system is affected by CsA.…”