Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1967 Mar 1;32(3):685–698. doi: 10.1083/jcb.32.3.685

CELLULAR MECHANISM OF INTESTINAL PERMEABILITY ALTERATIONS PRODUCED BY CHELATION DEPLETION

M M Cassidy 1, C S Tidball 1
PMCID: PMC2107279  PMID: 4962241

Abstract

The absorption of phenolsulfonphthalein (phenol red) was used as a measure in vivo of intestinal permeability in anesthetized rats. A chelating agent, sodium ethylenediaminetetraacetate (NaEDTA), placed in the lumen evoked a fivefold increase in membrane permeability; at the same time the mucosal content of magnesium and calcium decreased significantly. Making either magnesium or calcium available to the luminal surface of the membrane in isotonic solution restored normal permeability and brought the cation contents above the original levels. Electron micrographs of tissues treated in vivo with NaEDTA revealed (a) rounded swellings on the microvilli in the area of the junctional complexes between adjacent epithelial cells, (b) widening of intercellular channels particularly in the region of the intermediate junctions (zonulae adhaerentes), and (c) loss of architectural detail in the region of the desmosomes (maculae adhaerentes) with separation of their dense borders. All of these alterations in fine structure could be reversed by in vivo cation replacements which reinstated normal permeability. The implications of these findings on mechanisms of fluid transport across epithelial membranes are discussed, and a working hypothesis for the role of divalent cations in membrane permeability regulation is presented.

Full Text

The Full Text of this article is available as a PDF (1.4 MB).

Selected References

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

  1. DEHAAN R. L. The effects of the chelating agent ethylenediamine tetra-acetic acid on cell adhesion in the slime mould Dictyostelium discoideum. J Embryol Exp Morphol. 1959 Sep;7:335–343. [PubMed] [Google Scholar]
  2. Diamond J. M., Tormey J. M. Role of long extracellular channels in fluid transport across epithelia. Nature. 1966 May 21;210(5038):817–820. doi: 10.1038/210817a0. [DOI] [PubMed] [Google Scholar]
  3. FARQUHAR M. G., PALADE G. E. FUNCTIONAL ORGANIZATION OF AMPHIBIAN SKIN. Proc Natl Acad Sci U S A. 1964 Apr;51:569–577. doi: 10.1073/pnas.51.4.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. FARQUHAR M. G., PALADE G. E. Junctional complexes in various epithelia. J Cell Biol. 1963 May;17:375–412. doi: 10.1083/jcb.17.2.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Farquhar M. G., Palade G. E. Cell junctions in amphibian skin. J Cell Biol. 1965 Jul;26(1):263–291. doi: 10.1083/jcb.26.1.263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hays R. M., Singer B., Malamed S. The effect of calcium withdrawal on the structure and function of the toad bladder. J Cell Biol. 1965 Jun;25(3 Suppl):195–208. doi: 10.1083/jcb.25.3.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. LINDEMANN B., SOLOMON A. K. Permeability of luminal surface of intestinal mucosal cells. J Gen Physiol. 1962 Mar;45:801–810. doi: 10.1085/jgp.45.4.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. PALAY S. L., KARLIN L. J. An electron microscopic study of the intestinal villus. I. The fasting animal. J Biophys Biochem Cytol. 1959 May 25;5(3):363–372. doi: 10.1083/jcb.5.3.363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. REYNOLDS E. S. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol. 1963 Apr;17:208–212. doi: 10.1083/jcb.17.1.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. SCHANKER L. S., JOHNSON J. M. Increased intestinal absorption of foreign organic compounds in the presence of ethylenediaminetetraacetic acid (EDTA). Biochem Pharmacol. 1961 Dec;8:421–422. doi: 10.1016/0006-2952(61)90061-2. [DOI] [PubMed] [Google Scholar]
  11. SEDAR A. W., FORTE J. G. EFFECTS OF CALCIUM DEPLETION ON THE JUNCTIONAL COMPLEX BETWEEN OXYNTIC CELLS OF GASTRIC GLANDS. J Cell Biol. 1964 Jul;22:173–188. doi: 10.1083/jcb.22.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. SHNITKA T. K. CURRENT CONCEPTS OF THE PATHOGENESIS AND PATHOLOGY OF INFLAMMATORY LESIONS OF THE INTESTINE. Can Med Assoc J. 1964 Jul 4;91:7–22. [PMC free article] [PubMed] [Google Scholar]
  13. TIDBALL C. S. Active chloride transport during intestinal secretion. Am J Physiol. 1961 Feb;200:309–312. doi: 10.1152/ajplegacy.1961.200.2.309. [DOI] [PubMed] [Google Scholar]
  14. TIDBALL C. S. MAGNESIUM AND CALCIUM AS REGULATORS OF INTESTINAL PERMEABILITY. Am J Physiol. 1964 Jan;206:243–246. doi: 10.1152/ajplegacy.1964.206.1.243. [DOI] [PubMed] [Google Scholar]
  15. WHITTEMBURY G., SUGINO N., SOLOMON A. K. Effect of antidiuretic hormone and calcium on the equivalent pore radius of kidney slices from Necturus. Nature. 1960 Aug 20;187:699–701. doi: 10.1038/187699a0. [DOI] [PubMed] [Google Scholar]
  16. WINDSOR E., CRONHEIM G. E. Gastro-intestinal absorption of heparin and synthetic heparinoids. Nature. 1961 Apr 15;190:263–264. doi: 10.1038/190263a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES