Interaction of guanidinium and guanidinium derivatives with the Na+/H+ exchange system.
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 (K0.5 = 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 microM and 6 microM 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 45Ca2+ uptake by chick cardiac cells. Guanochlor does not compete with [3H]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.
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002478:Cells, Cultured; D002645:Chickens; D004285:Dogs; D005347:Fibroblasts; D019791:Guanidine; D006146:Guanidines / Q000378:metabolism / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000378:metabolism; D051379:Mice; D009132:Muscles / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; D019791:Guanidine; C012340:guanoclor; D002118:Calcium