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. 1984 Dec;25(12):1376–1379. doi: 10.1136/gut.25.12.1376

Inhibitory effect of unconjugated bile acids on the intestinal transport of 5-methyltetrahydrofolate in rat jejunum in vitro.

H M Said, D Hollander, W B Strum
PMCID: PMC1420213  PMID: 6510770

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ammon H. V. Effect of taurine conjugated bile salts with and without lecithin on water and electrolyte transport in the canine gallbladder in vivo. Gastroenterology. 1979 Apr;76(4):778–783. [PubMed] [Google Scholar]
  2. Barrett C. R., Jr, Holt P. R. Postgastrectomy blind loop syndrome. Megaloblastic anemia secondary to malabsorption of folic acid. Am J Med. 1966 Oct;41(4):629–637. doi: 10.1016/0002-9343(66)90226-9. [DOI] [PubMed] [Google Scholar]
  3. Bernstein L. H., Gutstein S., Weiner S. Folic acid conjugase: inhibition by unconjugated dihydroxy bile acids. Proc Soc Exp Biol Med. 1969 Dec;132(3):1167–1169. doi: 10.3181/00379727-132-34388. [DOI] [PubMed] [Google Scholar]
  4. DIXON M. The determination of enzyme inhibitor constants. Biochem J. 1953 Aug;55(1):170–171. doi: 10.1042/bj0550170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gorbach S. L., Mitra R., Jacobs B., Banwell J. G., Chatterjee B. D., Mazumder D. N. Bacterial contamination of the upper small bowel in tropical sprue. Lancet. 1969 Jan 11;1(7585):74–77. doi: 10.1016/s0140-6736(69)91091-5. [DOI] [PubMed] [Google Scholar]
  6. Hill M. J. Some leads to the etiology of cancer of the large bowel. Surg Annu. 1978;10:135–149. [PubMed] [Google Scholar]
  7. Hofmann A. F. The enterohepatic circulation of bile acids in man. Clin Gastroenterol. 1977 Jan;6(1):3–24. [PubMed] [Google Scholar]
  8. Isaacs P. E., Kim Y. S. Blind loop syndrome and small bowel bacterial contamination. Clin Gastroenterol. 1983 May;12(2):395–414. [PubMed] [Google Scholar]
  9. Kahn I. J., Jeffries G. H., Sleisenger M. H. Malabsorption in intestinal scleroderma. Correction by antibiotics. N Engl J Med. 1966 Jun 16;274(24):1339–1344. doi: 10.1056/NEJM196606162742402. [DOI] [PubMed] [Google Scholar]
  10. Lifshitz F., Wapnir R. A., Wehman H. J., Diaz-bensussen S., Pergolizzi R. The effects of small intestinal colonization by fecal and colonic bacteria on intestinal function in rats. J Nutr. 1978 Dec;108(12):1913–1923. doi: 10.1093/jn/108.12.1913. [DOI] [PubMed] [Google Scholar]
  11. Lindenbaum J. Aspects of vitamin B12 and folate metabolism in malabsorption syndromes. Am J Med. 1979 Dec;67(6):1037–1048. doi: 10.1016/0002-9343(79)90646-6. [DOI] [PubMed] [Google Scholar]
  12. Rosenberg I. H. Absorption and malabsorption of folates. Clin Haematol. 1976 Oct;5(3):589–618. [PubMed] [Google Scholar]
  13. Said H. M., Strum W. B. A pH-dependent, carrier-mediated system for transport of 5-methyltetrahydrofolate in rat jejunum. J Pharmacol Exp Ther. 1983 Jul;226(1):95–99. [PubMed] [Google Scholar]
  14. Schoenfield L. J., Lachin J. M. Chenodiol (chenodeoxycholic acid) for dissolution of gallstones: the National Cooperative Gallstone Study. A controlled trial of efficacy and safety. Ann Intern Med. 1981 Sep;95(3):257–282. doi: 10.7326/0003-4819-95-3-257. [DOI] [PubMed] [Google Scholar]
  15. Simon G. L., Gorbach S. L. Intestinal flora in health and disease. Gastroenterology. 1984 Jan;86(1):174–193. [PubMed] [Google Scholar]
  16. Strum W. B. Characteristics of the transport of pteroylglutamate and amethopterin in rat jejunum. J Pharmacol Exp Ther. 1981 Feb;216(2):329–333. [PubMed] [Google Scholar]
  17. Tabaqchali S., Booth C. C. Jejunal bacteriology and bile-salt metabolism in patients with intestinal malabsorption. Lancet. 1966 Jul 2;2(7453):12–15. doi: 10.1016/s0140-6736(66)91744-2. [DOI] [PubMed] [Google Scholar]
  18. Wingate D. L., Phillips S. F., Hofmann A. F. Effect of glycine-conjugated bile acids with and without lecithin on water and glucose absorption in perfused human jejunum. J Clin Invest. 1973 May;52(5):1230–1236. doi: 10.1172/JCI107290. [DOI] [PMC free article] [PubMed] [Google Scholar]

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