The Journal of Membrane Biology

, Volume 71, Issue 3, pp 219–226 | Cite as

Inhibition of chloride secretion by furosemide in canine tracheal epithelium

  • Michael J. Welsh


Furosemide inhibits Cl transport in a variety of epithelial and nonepithelial cells. To examine the mechanism of Cl secretion in canine tracheal epithelium, the effect of furosemide on transepithelial ion fluxes, membrane resistances, and electromotive forces was determined using intracellular microelectrodes and an equivalent electrical circuit analysis. There were six main observations: First, furosemide was only effective when added to the submucosal solution. Second, inhibition by furosemide (10−3m) was specific for Cl secretion with no effect on Na absorption. Third, furosemide produced a half-maximal inhibition of Cl secretion at a concentration of 7×10−6m. A Hill plot yielded a slope not different from unity, suggesting a one-for-one interaction of furosemide with the Cl transport process. Fourth, despite complete inhibition of Cl secretion, furosemide produced only small changes in transepithelial and apical membrane resistance, indicating that the primary effect was not an inhibition of Cl exit from the cell across the apical membrane. Fifth, basolateral membrane resistance and electromotive force were not altered by furosemide. This finding suggested that the effect of furosemide at the basolateral membrane was on an electrically neutral Cl entry process. Sixth, calculation of the intracellular Cl concentration from the electromotive force across the apical membrane indicated that furosemide decreased intracellular Cl concentration by 50%, consistent with an inhibition of Cl entry into the cell. These results indicate that Cl enters the epithelial cell via an electrically neutral process at the basolateral membrane and that furosemide selectively inhibits that process, resulting in a decreased intracellular Cl concentration and a decrease in the driving force for Cl exit across the apical membrane.

Key words

tracheal epithelium furosemide Cl secretion electrophysiology loop diuretic equivalent electrical circuit 


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  1. Al-Bazzaz, F.J., Al-Awqati, Q. 1979. Interaction between sodium and chloride transport in canine tracheal mucosa.J. Appl. Physiol. 46:111–119Google Scholar
  2. Al-Bazzaz, F., Yadava, V.P., Westenfelder, C. 1981. Modification of Na and Cl transport in canine tracheal mucosa by prostaglandins.Am. J. Physiol. 240:F101-F105Google Scholar
  3. Brazy, P.C., Gunn, R.B. 1976. Furosemide inhibition of chloride transport in human red blood cells.J. Gen. Physiol. 68:583–599Google Scholar
  4. Burg, M., Stone, L., Cardinal, J., Green, N. 1973. Furosemide effect on isolated perfused tubules.Am. J. Physiol. 225:119–124Google Scholar
  5. Candia, O.A. 1973. Short-circuit current related to active transport of chloride in frog cornea: Effects of furosemide and ethacrynic acid.Biochim. Biophys. Acta 298:1011–1014Google Scholar
  6. Candia, O.A., Schoen, H.F., Low, L., Podos, S.M. 1981. Chloride transport inhibition by piretanide and MK-196 in bullfrog corneal epithelium.Am. J. Physiol. 240:F25-F29Google Scholar
  7. Davis, B., Ueki, I., Bruderman, M.M., Nadel, J.A. 1977. Submucosal action of furosemide on chloride ion movement across canine tracheal epithelium.Am. Rev. Resp. Dis. 115:320Google Scholar
  8. Degnan, K.J., Karnaky, K.J., Zadunaisky, J.A. 1977. Active chloride transport in thein vitro opercular skin of a teleost (Fundulus heteroclitus), a gill-like epithelium rich in chloride cells.J. Physiol. (London) 251:155–191Google Scholar
  9. Eveloff, J., Kinne, R., Kinne-Saffran, E., Murer, H., Silva, P., Epstein, F.H., Stoff, J., Kinter, W.B. 1978. Coupled sodium and chloride transport into plasma membrane vesicles prepared from dogfish rectal gland.Pfluegers Arch. 378:87–92Google Scholar
  10. Frizzell, R.A., Field, M., Schultz, S.G. 1979. Sodium-coupled chloride transport by epithelial tissues.Am. J. Physiol. 236:F1-F8Google Scholar
  11. Frizzell, R.A., Smith, P.L., Vosburgh, E., Field, M. 1979. Coupled sodium-chloride influx across brush border of flounder intestine.J. Membrane Biol. 46:27–39Google Scholar
  12. Frömter, E., Gebler, B. 1977. Electrical properties of amphibian urinary bladder epithelia. III. The cell membrane resistances and the effect of amiloride.Pfluegers Arch. 371:99–108Google Scholar
  13. Geck, P., Pietrzyk, C., Burckhardt, B.-C., Pfeiffer, B., Heinz, E. 1980. Electrically silent co-transport of Na, K and Cl in Ehrlich cells.Biochim. Biophys. Acta 600:432–447Google Scholar
  14. Olver, R.E., Davis, B., Marin, M.G., Nadel, J.A. 1975. Active transport of Na+ and Cl across the canine tracheal epitheliumin vitro.Am. Rev. Resp. Dis. 112:811–815Google Scholar
  15. Reuss, L., Finn, A.L. 1975. Electrical properties of the cellular transepithelial pathway inNecturus gallbladder. I. Circuit analysis and steady-state effects of mucosal solution ionic substitutions.J. Membrane Biol. 25:115–139Google Scholar
  16. Russell, J.M. 1979. Chloride and sodium influx: A coupled uptake mechanism in the squid giant axon.J. Gen. Physiol. 73:801–818Google Scholar
  17. Saito, Y., Itoi, K., Horiuchi, K., Watanabe, T. 1980. Mode of action of furosemide on the chloride-dependent shortcircuit current across the ciliary body epithelium of toad eyes.J. Membrane Biol. 53:85–93Google Scholar
  18. Schultz, S.G., Frizzell, R.A., Nellans, H.N. 1977. Active sodium transport and the electrophysiology of rabbit colon.J. Membrane Biol. 33:351–384Google Scholar
  19. Silva, P., Stoff, J., Field, M., Fine, L., Forrest, J.N., Epstein, F. 1977. Mechanisms of active chloride secretion by shark rectal gland: Role of Na−K-ATPase in chloride transport.Am. J. Physiol. 233:F298-F306Google Scholar
  20. Smith, P.L., Welsh, M.J., Stoff, J.S., Frizzell, R.A. 1982. Chloride secretion by canine tracheal epithelium: I. Role of intracellular cAMP levels.J. Membrane Biol. 70:217–226Google Scholar
  21. Welsh, M.J., Smith, P.L., Frizzell, R.A. 1981. Intracellular chloride activities in the isolated perfused shark rectal gland.Clin. Res. 29:480A Google Scholar
  22. Welsh, M.J., Smith, P.L., Frizzell, R.A. 1982. Chloride secretion by canine tracheal epithelium. II. The cellular electrical potential profile.J. Membrane Biol. 70:227–238Google Scholar
  23. Welsh, M.J., Smith, P.L., Frizzell, R.A. 1983. Chloride secretion by canine tracheal epithelium: III. Membrane resistances and electromotive forces.J. Membrane Biol. 71:209–218Google Scholar
  24. Welsh, M.J., Widdicombe, J.H. 1980. Pathways of ion movement in the canine tracheal epithelium.Am. J. Physiol. 239:F215-F221Google Scholar
  25. Westenfelder, C., Earnest, W.R., Al-Bazzaz, F.J. 1980. Characterization of Na−K-ATPase in dog tracheal epithelium: Enzymatic and ion transport measurements.J. Appl. Physiol. 48:1008–1019Google Scholar
  26. Widdicombe, J.H., Basbaum, C.B., Highland, E. 1981. Ion contents and other properties of isolated cells from dog tracheal epithelium.Am. J. Physiol. 241:C184-C192Google Scholar
  27. Widdicombe, J.H., Ueki, I.F., Bruderman, I., Nadel, J.A. 1979. The effects of sodium substitution and ouabain on ion transport by dog tracheal epithelium.Am. Rev. Resp. Dis. 120:385–392Google Scholar
  28. Widdicombe, J.H., Welsh, M.J. 1980. Ion transport by dog tracheal epithelium.Fed. Proc. 39:3062–3066Google Scholar
  29. Wills, N.K., Lewis, S.A., Eaton, D.C. 1979. Active and passive properties of rabbit descending colon: A microelectrode and nystatin study.J. Membrane Biol. 45:81–108Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1983

Authors and Affiliations

  • Michael J. Welsh
    • 1
  1. 1.Pulmonary Division, Department of Internal MedicineUniversity of Iowa HospitalsIowa City

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