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

D. J. Benos, S. A. Simon, L. J. Mandel, Peter M Cala

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

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: The charged form of amiloride is the biologically active species. 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. 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. Amiloride can bind to and alter the charge on membrane surfaces, but this action cannot explain its highly specific effects in biological systems.

Original languageEnglish (US)
Pages (from-to)43-63
Number of pages21
JournalJournal of General Physiology
Volume68
Issue number1
StatePublished - 1976
Externally publishedYes

ASJC Scopus subject areas

  • Physiology

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