Open AccessInteraction of guanidinium and guanidinium derivatives with the Na + /H + exchange system
Author(s) -
FRELIN Christian,
VIGNE Paul,
BARBRY Pascal,
LAZDUNSKI Michel
Publication year - 1986
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1986.tb09388.x
Subject(s) - amiloride , chemistry , ouabain , biophysics , ion exchange , sodium , stereochemistry , ion , biology , organic chemistry
Guanidinium, a small organic monovalent cation that is permeant through voltage‐dependent cationic channels cannot be transported by the cardiac Na + /H + exchange system. Yet it recognizes the exchanger and is able to block its activity (K 0.5 = 30 mM). Guanidinium derivatives that do not belong to the amiloride series and which possess potent antihypertensive properties also block the activity of the Na + /H + exchange system in various cell types with a greater potency than unsubstituted guanidinium. The most potent compound found, guanochlor, has an affinity for the exchanger ranging between 0.5 μM and 6 μM in different systems and is more potent than amiloride in all systems studied. Guanochlor has the same action as amiloride derivatives on the cardiac cells; it prevents intracellular pH recovery in cardiac cells that have been acidified and also antagonizes the effect of ouabain on 45 Ca 2+ uptake by chick cardiac cells. Guanochlor does not compete with [ 3 H]ethylpropylamiloride for its binding to the Na + /H + exchange system of rabbit kidney brush border membrane. It is suggested that guanochlor recognizes a binding site on the Na + /H + exchanger that is distinct from the amiloride binding site.