Hepatic uptake and intestinal absorption of bile acids in the rabbit

Abstract

Abstract. The existence of transoorters for bile acidsIntroduction (BA) in liver and intestine has been well documented, but information is still needed as to their respective transport capacity. In the present investigation, we compared the hepatic and intestinal transport rates for BA, using perfused livers and intestines. The livers and intestines were separately perfused and doseresponse curves (0.25-10 mM) for tauroursodeoxycholate, taurocholate and taurodeoxycholate were obtained. The intestinal and mesenteric concentration and bile acid pattern were also evaluated in six non-fasting rabbits. Taurocholic, tauroursodeoxycholic and taurodeoxycholic acid ileal absorption showed saturation kinetics in the intestine as in the liver; the maximal uptake velocity for each bile acid in the liver was tenfold higher than the respective maximal transport velocity in the intestine; the Km values obtained in the liver were of the same order of magnitude, i.e. in the millimolar range. Taurocholic, tauroursodeoxycholic and taurodeoxycholic acid transport differences in the liver paralleled those in the intestine. Although the intestine was not homogeneously filled, the bile acid concentration in the ileal content fell into the range of the Km for the three studied bile acids, while the portal blood total bile acid concentration was inferior to the observed Kms of liver uptake. Therefore, both the hepatic and intestinal systems do not operate at their maximal transport rates at the prevailing concentrations in portal blood and luminal content, and the hepatic transport occurs at its highest efficiency (below the Km values) in physiological conditions. Both the liver and the intestine have been considered as main steps in the conservation of the enterohepatic circulation (EHC) of bile acids [l]. In the liver, the transport from the portal blood into bile requires distinct systems for uptake [2] and export across the apical membrane [3]. Also, different systems for transport across the basolateral and apical membrane [4] of intestinal cells operate. Therefore, the overall rate of bile acids (BA) extraction is the resultant of many processes. The kinetic parameters of the hepatic uptake of bile acids have been measured [5,6] and several systems have been identified and described in the liver [7-1 I], while an active absorption system for BA localized in the terminal ileum has been identified [12-191. It has been pointed out that besides active absorption in the ileum, passive diffusion in the jejunum helps maintain the EHC of BA [20]. Recent studies from our laboratory [21], moreover, have stressed the relative contribution of the active and passive route in the intestinal absorption of BA. These studies demonstrated that the passive component is limited mostly to dihydroxy unconjugated BA, while the transfer rates of conjugated bile acids from the lumen to the intestinal blood are largely dependent on active processes. Thus, in normal physiological conditions, where little amounts of unconjugated BA are present in the intes...

Weanling, but not adult, rabbit colon absorbs bile acids: flux is linked to expression of putative bile acid transporters

“…TC was selected because it is readily available commercially and has been utilized in a number of studies to examine intestinal absorption in the rabbit (3); however, the major bile acids reported in the rabbit circulation are secondary bile acids, especially glycodeoxycholic acid (20). Another reason 3 H-labeled TC is an appropriate marker is that, in a perfused rabbit model, ileal and hepatic rates of saturable uptake were much greater for TC than for TDC (2). TC caused a slight, but significant, increase in G t (14%) in weanling ileum, but not in any of the other tissues examined (Figs.…”

“…GAPDH is equally expressed in rabbit intestinal tissues of all age groups (see Figs. [1][2][3][4][5] and served as an internal control.…”

Targeted Deletion of the Ileal Bile Acid Transporter Eliminates Enterohepatic Cycling of Bile Acids in Mice

“…Several observations support the concept that the terminal ileum is the major site of bile acid reabsorption, including the finding that there is little decrease in intraluminal bile acid concentration prior to the ileum (5) and the appearance of bile acid malabsorption after ileal resection (6). More recent studies using in situ perfused intestinal segments to measure bile acid absorption (7)(8)(9) have also demonstrated that ileal active bile acid transport is a high capacity system sufficient to account for the biliary output of bile acids. Finally, patients with a rare inherited Slc10a2 defect exhibit bile acid malabsorption, refractory infantile diarrhea, steatorrhea, and failure to thrive (primary bile acid malabsorption), underscoring the importance of Slc10a2 in the human infant (10,11).…”

Intestinal transport and metabolism of bile acids

“…The general consensus from numerous studies is that ileal active transport is the major route for conjugated bile acid uptake, whereas the passive or facilitative absorption present along the length of the small intestine may be signifi cant for unconjugated and some glycine-conjugated bile acids ( 34,35,(40)(41)(42). Although bile acids in most vertebrates are conjugated to taurine, the bile acid pool of humans includes a signifi cant proportion of glycine conjugates ( 43,44 ).…”