INFERENCES ON THE NATURE OF THE APICAL SODIUM ENTRY SITE IN FROG-SKIN EPITHELIUM

  • 1 January 1981
    • journal article
    • research article
    • Vol. 219  (2) , 481-488
Abstract
The inhibition and stimulation of short-circuit current in in vitro frog skin by a series of structural analogs of the diuretic amiloride were studied. The inhibitory profile of a new experimental diuretic, 3-(3-amino-1,2,4-oxadiazol-5-yl)-5-chloro-2,6-pyrazinediamine, or CGS 4270, was determined. The major conclusions are: amiloride remains the most effective inhibitor of Na+ entry, with both the pyrazine ring and the acylguanidine moiety being required for maximum activity; CGS 4270 also inhibits Na+ transport in frog skin; it acts only from the external solution, is uncharged, is noncompetitive with Na+ and interacts noncompetitively with amiloride; the inhibition is independent of external Ca; and benzimidazole increases amiloride-sensitive short-circuit current and this compound is competitive with amiloride. The putative Na+ entry protein may contain multiple inhibitory sites and compounds which stimulate Na+ entry may also bind at the same molecular locus as an inhibitor.