Effect of amiloride and some of its analogues of cation transport in isolated frog skin and thin lipid membranes.

Journal Article (Journal Article)

The inhibition of short-circuit current (Isc) in isolated frog skin and the induction of surface potentials in lipid bilayer membranes produced by the diuretic drug amiloride and a number of its chemical analogues was studied. The major conclusions of our study are: (a) The charged form of amiloride is the biologically active species. (b) Both the magnitude of Isc and the amiloride inhibitory effect are sensitive to the ionic milieu bathing the isolated skin, and these two features are modulated at separate and distinct regions on the transport site. (c) Amiloride is very specific in its inhibitory interaction with the Na+ transport site since slight structural modifications can result in significant changes in drug effectiveness. We found that substitutions at pyrazine ring position 5 greatly diminish drug activity, while changes at position 6 are less drastic. Alterations in the guanidinium moiety only diminish activity if the result is a change in the spatial orientation of the amino group carrying the positive charge. (d) Amiloride can bind to and alter the charge on membrane surfaces, but this action cannot explain its highly specific effects in biological systems.

Full Text

Duke Authors

Cited Authors

  • Benos, DJ; Simon, SA; Mandel, LJ; Cala, PM

Published Date

  • July 1, 1976

Published In

Volume / Issue

  • 68 / 1

Start / End Page

  • 43 - 63

PubMed ID

  • 7635

Pubmed Central ID

  • PMC2228413

International Standard Serial Number (ISSN)

  • 0022-1295

Digital Object Identifier (DOI)

  • 10.1085/jgp.68.1.43


  • eng

Conference Location

  • United States