Digestive Diseases and Sciences

, Volume 39, Issue 4, pp 796–801 | Cite as

Mechanisms and sites of mannitol permeability of small and large intestine in the rat

  • P. Krugliak
  • D. Hollander
  • C. C. Schlaepfer
  • H. Nguyen
  • T. Y. MA
Original Articles
Received:
Revised:
Accepted:

Abstract

Mannitol is commonly used as an intestinal permeability probe, yet the mechanisms of its penetration of the intestinal barrier are not entirely clear. Therefore, we studied mannitol's permeability of different segments of the intestine and studied the kinetics and influence of intraluminal factors on mannitol permeabilityin vivo in perfused intestinal segments of rats. There was linear relationship between permeability rate of mannitol and its luminal concentration (y=7.2x+1.7;r=0.98), indicating that passive diffusion is involved in mannitol's permeability. Increased luminal fluid osmolarity from 0.3 to 0.6 osmol/liter resulted in decreased net water flux with a corresponding decrease in mannitol permeability in both jejunum and colon (P<0.01), indicating the prominent influence of solvent drag on net mannitol permeability. The relationship between mannitol permeability and water absorption at different osmolarities was linear in the jejunum and colon. At luminal osmolarity of 0.3 osmol/liter, 34.6% of mannitol permeability was mediated by passive diffusion and 65.4% was mediated by solvent drag in the jejunum. Mannitol permeability was much more dependent on solvent drag in the colon (88.9%) than in the small intestine (65.4%). The net permeability rate of mannitol was similar in the jejunum and ileum but was much higher in the colon (P<0.01). Addition of chenodeoxycholate (5 mM) to the perfusate resulted in a significant decrease in absorption of water (P<0.01) with a corresponding decrease in mannitol permeability (P<0.01). These studies indicate that mannitol permeability of the intestinal barrier is mediated by passive diffusion and solvent drag, with the latter accounting for a greater fraction of the total permeability.

Key words

intestinal absorption intestinal permeability mannitol osmolarity water transport solvent drag intestinal barrier functions tight junction food antigens 
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References

  1. 1.
    Jenkins RT, Goodacre RL, Rooney PJ, Bienenstock J, Sivakumaran J, Walker WHC: Studies of intestinal permeability in inflammatory diseases using polyethylene glycol 400. Clin Biochem 19:298–302, 1986Google Scholar
  2. 2.
    Bjarnason I, Peters TJ, Veall N: A persistent defect in intestinal permeability in coeliac disease demonstrated by a51Cr-labelled EDTA absorption test. Lancet 1:323–325, 1983Google Scholar
  3. 3.
    Hamilton I, Cobden I, Rothwell J, Axon ATR: Intestinal permeability in coeliac disease: The response to gluten withdrawal and single-dose gluten challenge. Gut 23:202–210, 1982Google Scholar
  4. 4.
    Menzies IS, Laker MF, Pounder R, Bull J, Heyer S, Wheeler PG, Creamer B: Abnormal intestinal permeability to sugars in villous atrophy. Lancet 2:1107–1109, 1979Google Scholar
  5. 5.
    Jenkins RT, Rooney PJ, Jones DB, Bienenstock J, Goodacre RL: Increased intestinal permeability in patients with rheumatoid arthritis: A side-effect of oral nonsteroidal antiinflammatory drug therapy? Br J Rheumatol 26:103–107, 1987Google Scholar
  6. 6.
    Ukabam SO, Clamp JR, Cooper BT: Abnormal small intestinal permeability to sugars in patients with Crohn's disease of the terminal ileum and colon. Digestion 27:70–74, 1982Google Scholar
  7. 7.
    Sanderson IR, Boulton P, Menzies IS, Walker-Smith JA: Improvement of abnormal lactulose/rhamnose permeability in active Crohn's disease of the small bowel by an elemental diet. Gut 28:1073–1076, 1987Google Scholar
  8. 8.
    Bjarnason I, Zanelli G, Smith T, Prouse P, Williams P, Delacey G, Gumpel MJ, Levi AJ: Nonsteroidal antiinflammatory drug-induced intestinal inflammation in humans. Gastroenterology 93:480–489, 1987Google Scholar
  9. 9.
    Maxton DG, Bjarnason I, Reynolds AP, Catt SD, Peters TJ, Menzies IS: Lactulose,51Cr-EDTA, ethylenediaminetetraacetate,l-rhamnose and polyethylene glycol 500 as probe markers for assessmentin vivo of human intestinal permeability. Clin Sci 71:71–80, 1986Google Scholar
  10. 10.
    Chadwick VS, Phillips SF, Hofmann AF: Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). I. Chemical analysis and biological properties of PEG 400. Gastroenterology 73:241–246, 1977Google Scholar
  11. 11.
    Chadwick VS, Phillips SF, Hofmann AF: Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400) II. Application to normal and abnormal permeability states in man and animals. Gastroenterology 73:247–251, 1977Google Scholar
  12. 12.
    Laker MF, Bull HJ, Menzies IS: Evaluation of mannitol for use as a probe marker of gastrointestinal permeability in man. Eur J Clin Invest 12:485–491, 1982Google Scholar
  13. 13.
    Krugliak P, Hollander D, Tran D, Dadufalza VD, Katz KD, Le K: Mechanisms of polyethylene glycol 400 permeability in perfused rat intestine. Gastroenterology 97:1164–1170, 1989Google Scholar
  14. 14.
    Hollander D, Ricketts D, Boyd CAR: Importance of “probe” molecular geometry in determining intestinal permeability. Can J Gastroenterol 2(suppl A):35A-38A, 1988Google Scholar
  15. 15.
    Katz KD, Hollander D, Vadheim CM, McElree C, Delahunty T, Dadufalza VD, Krugliak P, Rotter JI: Intestinal permeability in patients with Crohn's disease and their healthy relatives. Gastroenterology 97:927–931, 1989Google Scholar
  16. 16.
    Hollander D: The intestinal permeability barrier. A hypothesis as to its regulation and involvement in Crohn's disease. Scand J Gastroenterol 27:721–726, 1992Google Scholar
  17. 17.
    Miller DL, Schedl HP: Total recovery studies of nonabsorable indicators in the rat small intestine. Gastroenterology 58:40–46, 1970Google Scholar
  18. 18.
    Hollander D: Intestinal absorption of vitamins A, E, D, and K. J Lab Clin Med 97:449–462, 1981Google Scholar
  19. 19.
    Meshkinpour H, Smith M, Hollander D: Influence of aging on the surface area of the small intestine in the rat. Exp Gerontol 16:399–404, 1981Google Scholar
  20. 20.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275, 1951Google Scholar
  21. 21.
    Krugliak P, Hollander D, Le K, Ma T, Dadufalza VD, Katz KD: Regulation of polyethylene glycol 400 intestinal permeability by endogenous and exogenous prostanoids. Influence of non-steroidal anti-inflammatory drugs. Gut 31:417–421, 1990Google Scholar
  22. 22.
    Schafer JA, Andreoli TE: Principles of water and nonelectrolyte transport across membranes.In Physiology of Membrane Disorders. TE Andreoli, JF Hofmann, DD Fanestil, SG Schultz (eds). New York, Plenum, 1986, pp 177–190Google Scholar
  23. 23.
    Capraro V: Permeability and related phenomena: Basic concepts.In Pharmacology of Intestinal Permeation I. TZ Csaky (eds). Berlin, Springer-Verlag, 1984, pp 61–89Google Scholar
  24. 24.
    Pappenheimer JR, Reiss KZ: Contribution of solvent drag through intercellular junctions to absorption of nutrients by the small intestine of the rat. J Membr Biol 100:123–136, 1987Google Scholar
  25. 25.
    Chadwick VS, Gaginella TS, Carlson GL, Debongnie JC, Phillips SF, Hofmann AF: Effect of molecular structure on bile acid-induced alterations in absorptive function, permeability, and morphology in the perfused rabbit colon. J Lab Clin Med 94:661–674, 1979Google Scholar
  26. 26.
    Pappenheimer JR: Paracellular intestinal absorption of glucose, creatinine, and mannitol in normal animals: relation to body size. Am J Physiol 259:G290–G299, 1990Google Scholar
  27. 27.
    Powell DW, Malaner SJ: Relationship between water and solute transport from isosmotic solutions by rat intestinein vivo. Am J Physiol 215:49–55, 1968Google Scholar
  28. 28.
    Ammon HV, Tapper EJ, Komorowski RA, Charaf UK, Loeffler RF, Lewand D, Walter LG: Effects of sulfodeoxycholate on rat and rabbit small intestine. Am J Physiol 248:G485–G493, 1985Google Scholar

Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • P. Krugliak
    • 1
  • D. Hollander
    • 1
  • C. C. Schlaepfer
    • 1
  • H. Nguyen
    • 1
  • T. Y. MA
    • 1
  1. 1.From the Division of Gastroenterology, Department of MedicineUniversity of CaliforniaIrvine

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