CROSS-REACTIVITY OF AMILORIDE AND 2,4,6 TRIAMINOPYRIMIDINE (TAP) FOR THE CELLULAR ENTRY AND TIGHT JUNCTIONAL CATION PERMEATION PATHWAYS IN EPITHELIA

2,4,6 Triaminopyrimidine (TAP) inhibits the passive tight junctional cation permeation pathway in various leaky epithelia. Amiloride inhibits the cation cellular entry pathway in tight epithelia. TAP and amiloride at appropriate concentrations are able to block either of these epithelial cation permeation pathways. TAP blocks the NA entry pathway in frog skin. It inhibits from the external solution only, is completely reversible, increases the transepithelial resistance, is active in the monoprotonated form, is noncompetitive with Na, displays saturation kinetics which obey a simple kinetic model (KI = 1 .times. 10-3 M), is independent of external Ca, is dependent on external buffering capacity and is competitive with amiloride. Amiloride inhibition of the junctional permeation in gallbladder increases the transepithelial resistance, decreases cation conductance without affecting the anion conductance, displays saturation kinetics which obey a simple kinetic model (KI = 1 .times. 10-3 M) and possesses inhibitory activity in both its protonated and unprotonated form. A similar inhibitory site may exist in both cation permeation pathways, and the chemical nature and possible location of these inhibitory sites is provided.