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Effect of amiloride on sodium transport in the proximal, distal, and entire human colonin vivo

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Abstract

In vitrostudies under short-circuited conditions suggest that amiloride, a diuretic agent which is thought to block apical membrane sodium entry, has significant effects on sodium absorption by the human colon. To evaluate this in vivo,we studied the effect of amiloride applied in concentrations of 10−5 and 10 −4 M on sodium transport and potential difference (PD) in human colon during steadystate perfusion. Net sodium absorption was reduced 25% by amiloride and chloride absorption by 15%; potassium and bicarbonate secretion rates were enhanced. In other studies the colon was divided into a proximal and distal test segment by endoscopic introduction of a collection channel to the descending colonsigmoid junction. Comparison of tritiated water absorption by the two segments indicated that the distal segment comprised approximately 20% of the total colon surface area. However, the distal test segment only accounted for 5–7% of total sodium, chloride, or water absorption; in contrast, 17–20% of total potassium or bicarbonate secretion occurred there. In the proximal test segment, amiloride reduced net sodium absorption by almost one third from 21.0 to 14.4 mmollhr (P<0.02) but had no significant effect on PD. In the distal test segment, amiloride produced a 25% reduction in mean sodium absorption from 1.2 to 0.9 mmollhr, but this reduction was not statistically significant;however, potential difference was significantly reduced by 33% (P<0.02). These results suggest that most sodium absorption in normal human colon in vivois mediated by transport processes which are insensitive to these doses of amiloride. An effect of amiloride on potential difference was only evident in the distal colon, suggesting differences in the transport processes or in the permeability properties of the proximal and distal colon in vivo.

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References

  1. Schultz SG: Ion transport by mammalian large intestine.In Physiology of the Gastrointestinal Tract. LR Johnson (ed). New York, Raven Press, 1981, pp 991–1002

    Google Scholar 

  2. Binder HJ: Absorption and secretion of water and electrolytes by small and large intestine.In Gastrointestinal Disease: Pathophysiology, Diagnosis, Management, 3rd ed. MH Sleisenger, JS Fordtran (eds). Philadelphia, WB Saunders, 1983, pp 811–829

    Google Scholar 

  3. Bridges RJ, Rummel W: Mechanistic basis of alterations in mucosal water and electrolyte transport. Clin Gastroenterol 15:491–506, 1986

    PubMed  Google Scholar 

  4. Binder HJ, Rawlins CL: Electrolyte transport across isolated large intestinal mucosa. Am J Physiol 225:1232–1239, 1973

    PubMed  Google Scholar 

  5. Stoebel DP, Goldner AM: Ion transport across the rat colon. Physiologist 18:410, 1975

    Google Scholar 

  6. Frizzell RA, Koch MJ, Schultz SG: Ion transport by rabbit colon: I. Active and passive components. J Membr Biol 27:297–316, 1976

    PubMed  Google Scholar 

  7. Schultz SG, Frizzell RA, Nellans HN: Active sodium transport and the electrophysiology of rabbit colon. J Membr Biol 33:351–384, 1977

    PubMed  Google Scholar 

  8. Frizzell RA, Turnheim K: Ion transport by rabbit colon: II. Unidirectional sodium influx and the effects of amphotericin B and amiloride. J Membr Biol 40:193–211, 1978

    PubMed  Google Scholar 

  9. Binder HJ, Foster ES, Budinger ME, Hayslett JP: Mechanism of electroneutral sodium chloride absorption in distal colon of the rat. Gastroenterology 93:449–455, 1987

    PubMed  Google Scholar 

  10. Grady GF, Duhamel RC, Moore EW: Active transport of sodium by human colonin vitro. Gastroenterology 59:583–588, 1970

    PubMed  Google Scholar 

  11. Archampong EQ, Harris J, Clark CG: The absorption and secretion of water and electrolytes across the healthy and the diseased human colonic mucosa measuredin vitro. Gut 13:880–886, 1972

    PubMed  Google Scholar 

  12. Rask-Madsen J, Hjelt K: Effect of amiloride on electrical activity and electrolyte transport in human colon. Scand J Gastroenterol 12:1–6, 1977

    PubMed  Google Scholar 

  13. Hawker PC, Mashiter KE, Turnberg LA. Mechanisms of transport of Na, Cl, and K in the human colon. Gastroenterology 74:1241–1247, 1978

    PubMed  Google Scholar 

  14. Sandle GI, Wills NK, Alles W, Binder HJ: Electrophysiology of the human colon: Evidence of segmental heterogeneity. Gut 27:999–1005, 1986

    PubMed  Google Scholar 

  15. Hubel KA, Renquist K, Shirazi S: Ion transport in human cecum, transverse colon, and sigmoid colonin vitro: Baseline and response to electrical stimulation of intrinsic nerves. Gastroenterology 92:501–507, 1987

    PubMed  Google Scholar 

  16. Sellin JH, DeSoigne R: Ion transport in human colonin vitro. Gastroenterology 93:441–448, 1987

    PubMed  Google Scholar 

  17. Cuthbert AW: Characteristics of sodium channels in transporting epithelia.In Amiloride and Epithelial Sodium Transport. AW Cuthbert, GM Fanelli Jr, A Scriabine (eds). Baltimore, Urban and Schwarzenberg, 1979, pp 173–184

    Google Scholar 

  18. Benos DJ: Amiloride: A molecular probe of sodium transport in tissues and cells. Am J Physiol 242:C131-C145, 1982

    PubMed  Google Scholar 

  19. Fromm M, Hegel U: Segmental heterogeneity of epithelial transport in rat large intestine. Pflugers Arch 378:71–83, 1978

    PubMed  Google Scholar 

  20. Sellin JH, DeSoignie R: Rabbit proximal colon: A distinct transport epithelium. Am J Physiol 246:G603-G610, 1984

    PubMed  Google Scholar 

  21. Sellin JH, DeSoignie RC: Steroids alter ion transport and absorptive capacity in proximal and distal colon. Am J Physiol G113–G119, 1985

  22. Will PC, Lebowitz JL, Hopfer U: Induction of amiloridesensitive sodium transport in the rat colon by mineralocorticoids. Am J Physiol 238:F261-F268, 1980

    PubMed  Google Scholar 

  23. Levitan R, Fordtran JS, Burrows BA, Ingelfinger FJ: Water and salt absorption in the human colon. J Clin Invest 41:1754–1759, 1962

    PubMed  Google Scholar 

  24. Devroede GJ, Phillips SF: Failure of the human rectum to absorb electrolytes and water. Gut 11:438–442, 1970

    PubMed  Google Scholar 

  25. Devroede GJ, Phillips SF, Code CF, Lind JF: Regional differences in rates of insorption of sodium and water from the human large intestine. Can J Physiol Pharmacol 49:1023–1029, 1971

    PubMed  Google Scholar 

  26. Rask-Madsen J: Simultaneous measurement of electrical polarization and electrolyte transport by the entire normal and inflammed human colon duringin vivo perfusion. Scand J Gastroenterol 8:327–336, 1973

    PubMed  Google Scholar 

  27. Schiller LR, Davis GR, Santa Ana CA, Morawski SG, Fordtran JS: Studies of the mechanism of the antidiarrheal effect of codeine. J Clin Invest 70:999–1008, 1982

    PubMed  Google Scholar 

  28. Fordtran JS, Rector FS Jr, Carter NW: The mechanisms of sodium absorption in the human small intestine. J Clin Invest 47:884–900, 1968

    PubMed  Google Scholar 

  29. Hyden S: A turbidometric method for the determination of higher polyethylene glycols in biological materials. Lantbrukshogsk Ann 22:139–145, 1955

    Google Scholar 

  30. Fordtran JS: Marker perfusion techniques for measuring intestinal absorption in man. Gastroenterology 51:1089–1093, 1966

    PubMed  Google Scholar 

  31. Fordtrah JS, Rector FC Jr, Ewton MF, Soter N, Kinney J: Permeability characteristics of the human small intestine. J Clin Invest 66:1326–1333, 1965

    Google Scholar 

  32. Lewis LD, Fordtran JS: Effect of perfusion rate on absorption, surface area, unstirred water layer thickness, permeability, and intraluminal pressure in the rat ileumin vivo. Gastroenterology 68:1509–1516, 1975

    PubMed  Google Scholar 

  33. Davis GR, Santa Ana CA, Morawski SG, Fordtran JS: Permeability characteristics of human jejunum, ileum, proximal colon and distal colon: Results of potential difference measurements and unidirectional fluxes. Gastroenterology 83:844–850, 1982

    PubMed  Google Scholar 

  34. Wills NK, Alles WP, Sandle GI, Binder HJ: Apical membrane properties and amiloride binding kinetics of the human descending colon. Am J Physiol 247:G749-G757, 1984

    PubMed  Google Scholar 

  35. O'Neill RG, Boulpaep EL: Effect of amiloride on the apical cell membrane cation channels of a sodium-absorbing, potassium-secreting renal epithelium. J Membr Biol 50:365–387, 1979

    PubMed  Google Scholar 

  36. Baer JE, Jones CB, Spitzer SA, Russo HF: The potassium-sparing and natriuretic activity ofn-amidino-3,5,-diamino-6-chloropyrazinecarboxamide hydrochloride dihydrate (amiloride hydrochloride). J Pharmacol Exp Ther 157:472–485, 1967

    PubMed  Google Scholar 

  37. Benos DJ, Mandel LJ, Balaban RS: On the mechanism of the amiloride-sodium entry site interaction in anuran skin epithelia. J Gen Physiol 73:307–326, 1979

    PubMed  Google Scholar 

  38. Gordon LGM: Effect of amiloride on conductance of toad urinary bladder. J Membr Biol 52:61–67, 1980

    PubMed  Google Scholar 

  39. Labelle EF, Valentine ME: Inhibition by amiloride of22Na+ transport into toad bladder microsomes. Biochim Biophys Acta 601:195–205, 1980

    PubMed  Google Scholar 

  40. Heck GL, Mierson S, DeSimone JA: Salt taste transduction occurs through an amiloride-sensitive sodium transport pathway. Science 223:403–405, 1984

    PubMed  Google Scholar 

  41. Cremaschi D, Meyer G: Amiloride-sensitive sodium channels in rabbit and guinea-pig gallbadder. J Physiol 326:21–34, 1982

    PubMed  Google Scholar 

  42. Frederiksen O: Effect of amiloride on sodium and water reabsorption in the rabbit gallbladder. J Physiol 335:75–88, 1983

    PubMed  Google Scholar 

  43. Kinsella JL, Aronson PS: Amiloride inhibition of the Na+-H+ exchanger in renal microvillus membrane vesicles. Am J Physiol 241:F374-F379, 1981

    PubMed  Google Scholar 

  44. Dubinsky WP Jr, Frizzell RA: A novel effect of amiloride on H+-dependent Na+ transport. Am J Physiol 245:C157-C159, 1983

    PubMed  Google Scholar 

  45. LaBelle EF, Eaton DC. Amiloride-inhibited Na+ uptake into toad bladder microsomes in Na+-H+ exchange. Biochim Biophys Acta 733:194–197, 1983

    PubMed  Google Scholar 

  46. Frelin C, Vigne P, Lazdunski M: The role of the Na+/H+ exchange system in cardiac cells in relation to the control of the internal Na+ concentration. J Biol Chem 259:8880–8885, 1984

    PubMed  Google Scholar 

  47. Kurtin P, Charney AN: Effect of arterial carbon dioxide tension on amiloride-sensitive sodium absorption in the colon. Am J Physiol 247:G537-G541, 1984

    PubMed  Google Scholar 

  48. Binder HJ, Stange G, Murer H, Stieger B, Hauri HP: Sodium-proton exchange in colon brush border membranes. Am J Physiol 251:G382-G390, 1986

    PubMed  Google Scholar 

  49. Edmonds CJ: Amiloride sensitivity of the transepithelial electrical potential and of sodium and potassium transport in rat distal colonin vivo. J Physiol 313:547–559, 1981

    PubMed  Google Scholar 

  50. Turnheim K, Frizzell RA, Schultz SG: Interaction between cell sodium and the amiloride-sensitive sodium entry step in rabbit colon. J Membr Biol 39:233–256, 1978

    PubMed  Google Scholar 

  51. Mohamed F, McSorley P, Warren DJ: A comparison of methods for measurement of rectal potential difference in man: Effects of rectal infusion of amiloride. Clin Sci Mol Med 55:231–234, 1978

    PubMed  Google Scholar 

  52. Patton CJ, Jenkins MQ, Briggman JV, Spicer SS: Effect of amiloride on potential difference across rectal mucosa in cystic flbrosis patients. Pediatr Res 16:1035–1036, 1982

    PubMed  Google Scholar 

  53. Sandle GI, Gaiger E, Tapster S, Goodship THJ: Enhanced rectal potassium secretion in chronic renal insufficiency: Evidence for large intestinal potassium adaption in man. Clin Sci 71:393–401, 1986

    PubMed  Google Scholar 

  54. Colton T: Statistics in Medicine. Little, Brown, Boston, 1974

    Google Scholar 

  55. Blackenhorn DH, Hirsch J, Ahrens EH Jr: Transintestinal intubation: Technic for measurement of gut length and physiologic sampling at known loci. Proc Exp Biol Med 88:356–362, 1955

    Google Scholar 

  56. Foster ES, Hayslett JP, Binder HJ: Mechanism of active potassium absorption and secretion in the rat colon. Am J Physiol 246:G611-G617, 1984

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, Baylor University Medical Center, 3500 Gaston Avenue, 75246, Dallas, Texas

    Lawrence R. Schiller MD, Carol A. Santa Ana BS, Stephen G. Morawski BA & John S. Fordtran MD

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  1. Lawrence R. Schiller MD
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  2. Carol A. Santa Ana BS
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  3. Stephen G. Morawski BA
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  4. John S. Fordtran MD
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Additional information

This work was supported by U.S. Public Health Service grant 1-R01-AM37172-02 from the National Institute of Arthritis, Metabolism and Digestive Diseases, and a grant from the Southwestern Medical Foundation's Abbie K. Dreyfuss Fund, Dallas, Texas.

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Schiller, L.R., Santa Ana, C.A., Morawski, S.G. et al. Effect of amiloride on sodium transport in the proximal, distal, and entire human colonin vivo . Digest Dis Sci 33, 969–976 (1988). https://doi.org/10.1007/BF01535993

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  • DOI: https://doi.org/10.1007/BF01535993

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