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. 1985 Jul;26(7):704–709. doi: 10.1136/gut.26.7.704

Topical methotrexate alters solute and water transport in the rat jejunum in vivo and rabbit ileum in vitro.

C R Pinkerton, I W Booth, P J Milla
PMCID: PMC1433019  PMID: 4018634

Abstract

The topical effect of methotrexate (MTX) on small intestinal hexose and ion transport has been studied using an in vivo steady state jejunal perfusion technique in the rat, and short circuited rabbit terminal ileum in Ussing chambers in vitro. In rat jejunum, perfusion with MTX (1 mumol/l) caused significant reductions in water, sodium, and glucose absorption within 110 minutes of exposure. Fructose absorption was, however, unimpaired. The same concentration of MTX, when added to the mucosal side of distal rabbit ileum caused significant increases in transmucosal potential difference, short circuit current and the unidirectional flux of chloride from serosa to mucosa. In the presence of a subphysiological magnesium concentration (0.3 mmol/l), MTX resulted in the abolition of net sodium absorption and the conversion of net chloride absorption to secretion. We conclude that MTX has a topical effect on small intestinal transport which is independent of its effect on crypt cell kinetics.

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Selected References

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

  1. BOOTH C. C., BABOURIS N., HANNA S., MACINTYRE I. Incidence of hypomagnesaemia in intestinal malabsorption. Br Med J. 1963 Jul 20;2(5350):141–144. doi: 10.1136/bmj.2.5350.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baird G. M., Dossetor J. F. Methotrexate enteropathy. Lancet. 1981 Jan 17;1(8212):164–164. doi: 10.1016/s0140-6736(81)90760-1. [DOI] [PubMed] [Google Scholar]
  3. Bleyer W. A. The clinical pharmacology of methotrexate: new applications of an old drug. Cancer. 1978 Jan;41(1):36–51. doi: 10.1002/1097-0142(197801)41:1<36::aid-cncr2820410108>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  4. Booth I. W., Milla P. J., Harries J. T. The effects of magnesium on ion transport in short-circuited rabbit terminal ileum. Clin Sci (Lond) 1984 Apr;66(4):465–471. doi: 10.1042/cs0660465. [DOI] [PubMed] [Google Scholar]
  5. Craft A. W., Kay H., Lawson D. N., McElwain T. J. Methotrexate-induced malabsorption in children with acute lymphoblastic leukaemia. Br Med J. 1977 Dec 10;2(6101):1511–1512. doi: 10.1136/bmj.2.6101.1511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Field M., Fromm D., McColl I. Ion transport in rabbit ileal mucosa. I. Na and Cl fluxes and short-circuit current. Am J Physiol. 1971 May;220(5):1388–1396. doi: 10.1152/ajplegacy.1971.220.5.1388. [DOI] [PubMed] [Google Scholar]
  7. GOODNER C. J., MOORE T. E., Jr, BOWERS J. Z., ARMSTRONG W. D. Effects of acute whole-body x-irradiation on the absorption and distribution of Na22 and H3OH from the gastrointestinal tract of the fasted rat. Am J Physiol. 1955 Dec;183(3):475–484. doi: 10.1152/ajplegacy.1955.183.3.475. [DOI] [PubMed] [Google Scholar]
  8. Goldman I. D. Effects of methotrexate on cellular metabolism: some critical elements in the drug-cell interaction. Cancer Treat Rep. 1977 Jul;61(4):549–558. [PubMed] [Google Scholar]
  9. Gwavava N. J., Pinkerton C. R., Glasgow J. F., Sloan J. M., Bridges J. M. Small bowel enterocyte abnormalities caused by methotrexate treatment in acute lymphoblastic leukaemia of childhood. J Clin Pathol. 1981 Jul;34(7):790–795. doi: 10.1136/jcp.34.7.790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Harris I., Wilkinson A. W. Magnesium depletion in children. Lancet. 1971 Oct 2;2(7727):735–736. doi: 10.1016/s0140-6736(71)92104-0. [DOI] [PubMed] [Google Scholar]
  11. Jolly L. E., Jr, Fletcher H. P. The effect of repeated oral dosing of methotrexate on its intestinal absorption in the rat. Toxicol Appl Pharmacol. 1977 Jan;39(1):23–32. doi: 10.1016/0041-008x(77)90173-9. [DOI] [PubMed] [Google Scholar]
  12. Kaminskas E. Inhibition of sugar uptake by methotrexate in cultured Ehrlich ascites carcinoma cells. Cancer Res. 1979 Jan;39(1):90–95. [PubMed] [Google Scholar]
  13. Lewis I. J., Mainwaring D., Martin J. Enteropathy complicating maintenance therapy in acute lymphoblastic leukaemia. Arch Dis Child. 1982 Sep;57(9):663–667. doi: 10.1136/adc.57.9.663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Milla P. J., Atherton D. A., Leonard J. V., Wolff O. H., Lake B. D. Disordered intestinal function in glycogen storage disease. J Inherit Metab Dis. 1978;1(4):155–157. doi: 10.1007/BF01805585. [DOI] [PubMed] [Google Scholar]
  15. Pearson A. D., Craft A. W., Pledger J. V., Eastham E. J., Laker M. F., Pearson G. L. Small bowel function in acute lymphoblastic leukaemia. Arch Dis Child. 1984 May;59(5):460–465. doi: 10.1136/adc.59.5.460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pinkerton C. R., Cameron C. H., Sloan J. M., Glasgow J. F., Gwevava N. J. Jejunal crypt cell abnormalities associated with methotrexate treatment in children with acute lymphoblastic leukaemia. J Clin Pathol. 1982 Nov;35(11):1272–1277. doi: 10.1136/jcp.35.11.1272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pinkerton C. R., Glasgow J. F., Bridges J. M., Welshman S. G. Enterotoxic effect of methotrexate: does it influence the drug's absorption in children with acute lymphoblastic leukaemia? Br Med J (Clin Res Ed) 1981 Apr 18;282(6272):1276–1277. doi: 10.1136/bmj.282.6272.1276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pinkerton C. R., Welshman S. G., Dempsey S. I., Bridges J. M., Glasgow J. F. Absorption of methotrexate under standardized conditions in children with acute lymphoblastic leukaemia. Br J Cancer. 1980 Oct;42(4):613–615. doi: 10.1038/bjc.1980.286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. SCHULTZ S. G., ZALUSKY R. ION TRANSPORT IN ISOLATED RABBIT ILEUM. I. SHORT-CIRCUIT CURRENT AND NA FLUXES. J Gen Physiol. 1964 Jan;47:567–584. doi: 10.1085/jgp.47.3.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. SMALL M. D., CAVANAGH R. L., GOTTLIEB L., COLON P. L., ZAMCHECK N. The effect of aminopterin on the absorption of xylose from the rat small intestine. Am J Dig Dis. 1959 Sep;4:700–705. doi: 10.1007/BF02232175. [DOI] [PubMed] [Google Scholar]
  21. Sigrist-Nelson K., Hopfer U. A distinct D-fructose transport system in isolated brush border membrane. Biochim Biophys Acta. 1974 Oct 29;367(2):247–254. doi: 10.1016/0005-2736(74)90047-9. [DOI] [PubMed] [Google Scholar]
  22. Sladen G. E., Dawson A. M. Interrelationships between the absorptions of glucose, sodium and water by the normal human jejunum. Clin Sci. 1969 Feb;36(1):119–132. [PubMed] [Google Scholar]
  23. TAYLOR S. G., HASS G. M., CRUMRINE J. L., SLAUGHTER D. P. Toxic reactions of 4-amino-pteroylglutamic acid (aminopterin) in patients with far-advanced neoplastic disease. Cancer. 1950 May;3(3):493–503. doi: 10.1002/1097-0142(1950)3:3<493::aid-cncr2820030310>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  24. TRIER J. S. Morphologic alterations induced by methotrexate in the mucosa of human proximal intestine. I. Serial observations by light microscopy. Gastroenterology. 1962 Mar;42:295–305. [PubMed] [Google Scholar]
  25. Taminiau J. A., Gall D. G., Hamilton J. R. Response of the rat small-intestine epithelium to methotrexate. Gut. 1980 Jun;21(6):486–492. doi: 10.1136/gut.21.6.486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. VITALE J. J., ZAMCHECK N., DIGIORGIO J., HEGSTED D. M. Effects of aminopterin administration on the respiration and morphology of the gastrointestinal mucosa of rats. J Lab Clin Med. 1954 Apr;43(4):583–594. [PubMed] [Google Scholar]

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