Skip to main content
Log in

Mode of action of furosemide on the chloride-dependent short-circuit current across the ciliary body epithelium of toad eyes

  • Published:
The Journal of Membrane Biology Aims and scope Submit manuscript

Summary

The effects of furosemide on the chloride-dependent short-circuit current across the toad ciliary epithelium were examined. Under control conditions, the short-circuit current obeyed Michaelis-Menten kinetics against medium chloride concentration, the Michaelis constant (K m ) for chloride being 90mm and the maximal short-circuit current (V max) 128 μA/cm2. Furosemide added to the aqueous side of the epithelium rapidly reduced the short-circuit current; the effect was reversible. The effect of furosemide addition to the stromal side was much smaller and slower than that from the aqueous side. The dose-dependent range of furosemide action was from 0.1 μm to 1mm with 50% inhibition occurring at about 3 μm. Line-weaver-Burk plot of the short-circuit current against the chloride concentration showed that furosemide decreased the value ofV max and increased theK m ; the inhibition being of mixed type. A Hill plot of the dose-response curve yielding a slope of unity suggested one furosemide molecule combines with one chloride transport site. Probenecid, a competitive inhibitor of organic acid transport, reduced the effects of furosemide significantly when added simultaneously. The involvement of organic acid transport system in the mechanism of furosemide action on chloride transport was suggested.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Becker, B. 1960. The transport of organic anions by the rabbit eye. 1.In vitro iodopyracet (diodrast) accumulation by ciliary body-iris preprations.Am. J. Ophthalmol. 50:862

    Google Scholar 

  • Bindslev, N., Tormey, J.McD., Wright, E.M. 1974. The effects of electrical and osmotic gradients on lateral intercellular spaces and membrane conductance in a low resistance epithelium.J. Membrane Biol. 19:357

    Google Scholar 

  • Brazy, P.C., Gunn, R.B. 1976. Furosemide inhibition of chloride transport in human red blood cells.J. Gen. Physiol. 68:583

    Google Scholar 

  • Burg, M.B. 1976. Tubular chloride transport and the mode of action of some diuretics.Kidney Int 9:189

    Google Scholar 

  • Burg, M.B., Green, N. 1973. Function of the thick ascending limb of Henle's loop.Am. J. Physiol. 224:659

    Google Scholar 

  • Burg, M.B., Stoner, L., Cardinal, J., Green, N. 1973. Furosemide effect on isolated perfused tubules.Am. J. Physiol. 225:119

    Google Scholar 

  • 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

    Google Scholar 

  • Deetjen, P. 1966. Micropuncture studies on site and mode of diuretic action of furosemide.Ann. N.Y. Acad. Sci. 139:408

    Google Scholar 

  • Deuticke, B., Gerlach, E. 1967. Beeinflussung von Form und Phosphat-permeabilität menschlicher Erythrocyten durch Hämolysine, Benzol-derivate und pharmakologisch aktive Substanzen.Klin. Wochenschr. 45:977

    Google Scholar 

  • Dixon, M., Webb, E.C. 1964. Enzymes. p. 316. Longmans, London

    Google Scholar 

  • Ferguson, D.R., Twite, B.R. 1975. The effect of diuretics on Na+−K+-ATPase and c-AMP levels in toad bladder epithelial cells.Naunyn Schmiedeberg's Arch. Pharmacol. 287:111

    Google Scholar 

  • Field, M. 1977. Some speculations on the coupling between sodium and chloride transport processes in mammalian and teleost intestine.In: Membrane Transport Processes. J.F. Hoffman, editor. Vol. 1, p. 277. Raven Press, New York

    Google Scholar 

  • Forbes, M., Becker, B. 1960. The transport of organic anions by the rabbit eye. II.In vivo transport of iodopyracet (diodrast).Am. J. Ophthalmol. 50:867

    Google Scholar 

  • Frizzell, R.A., Heintze, K. 1979. Electrogenic chloride secretion by mammalian colon.In: Mechanisms of Intestinal Secretion. H.J. Binder, editor. p. 101. Alan R. Liss, New York

    Google Scholar 

  • Ginzburg, S.G., Hogg, J. 1967. What does a short-circuit current measure in biological systems?J. Theor. Biol. 14:316

    Google Scholar 

  • Goldstein, A., Aronow, L., Kalman, S.M. 1974. Principles of Drug Action: The Basis of Pharmacology. p. 82. John Wiley, New York

    Google Scholar 

  • Guelrud, M., Rudick, J., Janowitz, H.D. 1972. Effects of some inhibitors of sodium transport (adenosine triphosphatase inhibitors) on pancreatic secretion.Gastroenterology 62:540

    Google Scholar 

  • Holland, M.G. 1970. Chloride ion transport in the isolated ciliary body. II. Ion substitution experiments.Invest. Ophthalmol. 9:30

    Google Scholar 

  • Holland, M.G., Gipson, C.C. 1970. Chloride ion transport in the isolated ciliary body.Invest. Ophthalmol. 9:20

    Google Scholar 

  • Hook, J.B., Williamson, H.E. 1965a. Influence of probenecid and alterations in acid-base balance of the saluretic activity of furosemide.J. Pharmacol. Exp. Ther. 149:404

    Google Scholar 

  • Hook, J.B., Williamson, H.E. 1965b. Lack of correlation between natriuretic activity and inhibition of renal Na−K-activated ATPase.Proc. Soc. Exp. Biol. Med. 120:358

    Google Scholar 

  • Humphreys, M.H. 1976. Inhibition of NaCl absorption from perfused rat ileum by furosemide.Am. J. Physiol. 230:1517

    Google Scholar 

  • Rocha, A.S., Kokko, J.P. 1973. Sodium chloride and water transport in the medullary thick ascending limb of Henle: Evidence for active chloride transport.J. Clin. Invest. 52:612

    Google Scholar 

  • Sachs, J. 1971. Ouabain-insensitive sodium movements in human red blood cells.J. Gen. Physiol. 57:259

    Google Scholar 

  • Saito, Y., Watanabe, T. 1979. Relationship between short-circuit current and unidirectional fluxes of Na and Cl across the ciliary epithelium of the toad: Demonstration of active Cl transport.Exp. Eye Res. 28:71

    Google Scholar 

  • Schultz, S.G. 1979. Chloride transport by gastrointestinal epithelia: An overview.In Mechanisms of Intestinal Secretion. H.J. Binder, editor. p. 93. Alan R. Liss, New York

    Google Scholar 

  • Ussing, H.H., Zerahn, K. 1951. Active transport of sodium as the source of electric current in the short-circuited isolated frog skin.Acta Physiol. Scand. 23:110

    Google Scholar 

  • Watanabe, T., Saito, Y. 1978. Characteristics of ion transport across the isolated ciliary epithelium of the toad as studied by electrical measurements.Exp. Eye Res. 27:215

    Google Scholar 

  • Weiner, J.M., Washington, J.A., Mudge, G.H. 1960. On the mechanism of action of probenecid on renal tubular secretion.Bull. Johns Hopkins Hosp. 106:333

    Google Scholar 

  • Wright, E.M. 1974. Active transport of iodide and other anions across the choroid plexus.J. Physiol. (London) 240:535

    Google Scholar 

  • Zadunaisky, J.A. 1966. Active transport of chloride in frog cornea.Am. J. Physiol. 211:506

    Google Scholar 

  • Zadunaisky, J.A. 1972. Sodium activation of chloride transport in the frog cornea.Biochim. Biophys. Acta 282:255

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Department of Ophthalmology.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saito, Y., Itoi, K., Horiuchi, K. et al. Mode of action of furosemide on the chloride-dependent short-circuit current across the ciliary body epithelium of toad eyes. J. Membrain Biol. 53, 85–93 (1980). https://doi.org/10.1007/BF01870577

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01870577

Keywords

Navigation