title: Inhibitory effect of unconjugated bile acids on the intestinal transport of 5-methyltetrahydrofolate in rat jejunum in vitro.
abstract: The effect of the unconjugated bile acids, cholic, deoxycholic, chenodeoxycholic, and ursodeoxycholic acids, and of the conjugated bile acid taurocholic acid on the mucosal-to-serosal transport and tissue uptake of the naturally occurring folate derivative, 5-methyltetrahydrofolate (5-CH3H4PteGlu) was examined in everted sacs of rat jejunum. Each of the unconjugated bile acids examined inhibited the transport and tissue uptake of 5-CH3H4PteGlu in a concentration dependent manner. At low concentrations (0.01-0.1 mM) of cholic and deoxycholic acids, no structural or functional damage to the intestinal mucosa occurred and the transport of 5-CH3H4PteGlu was inhibited competitively with Ki values of 0.114 mM and 0.055 mM for cholic and deoxycholic acids, respectively. The greater inhibition of 5-CH3H4PteGlu transport by unconjugated bile acids at 1 mM can be attributed to observed structural and functional damage to the intestinal mucosa. The addition of 2 mM lecithin to the mucosal medium failed to prevent the inhibitory effect of 0.1 mM deoxycholic acid on the transport of 0.5 microM 5-CH3H4PteGlu. Compared with the effect of unconjugated bile acids, the conjugated bile acid taurocholic acid (0.01-5 mM) showed no effect on the transport and tissue uptake of 5-CH3H4PteGlu. The results of this study show that intestinal transport and tissue uptake of 5-CH3H4PteGlu are inhibited by unconjugated bile acids in a dose-dependent fashion. The clinical and physiological implications of these observations are discussed.
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D019826:Cholic Acid; D002793:Cholic Acids / Q000494:pharmacology; D003840:Deoxycholic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000494:pharmacology; D013763:Tetrahydrofolates / Q000378:metabolism*; D013997:Time Factors; D014580:Ursodeoxycholic Acid / Q000494:pharmacology
chemical_list: D001647:Bile Acids and Salts; D002793:Cholic Acids; D013763:Tetrahydrofolates; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D013656:Taurocholic Acid; D014580:Ursodeoxycholic Acid; D019826:Cholic Acid; C005984:5-methyltetrahydrofolate