title: Inhibition and activation of Na+-Ca2+ exchange activity by quinacrine.
abstract: Quinacrine either inhibited or stimulated Na-Ca exchange in cardiac sarcolemmal vesicles, depending on the experimental conditions. When present in the assay medium for Na-Ca exchange, quinacrine inhibited both Nai-dependent Ca2+ uptake (Ki = 50 microM) and Nao-dependent Ca2+ efflux. Quinacrine's inhibition of Ca2+ efflux was attenuated by high concentrations of Na+. Quinacrine also blocked Na-Na and Ca-Ca exchange activities in the vesicles. The inhibitory effects of quinacrine on Na-Ca exchange activity are qualitatively similar to those reported previously for amiloride derivatives. When Na-loaded vesicles were preincubated with quinacrine and then assayed for Na-Ca exchange in a quinacrine-free medium, stimulation of exchange activity was observed. This stimulation was reversible on the removal of bound quinacrine and involved in a reduction in the apparent Km for extravesicular Ca2+. Stimulation of exchange activity under these conditions was also observed with the lipophilic cation tetraphenylphosphonium. Since Ca2+, quinacrine and tetraphenylphosphonium all bind strongly to sarcolemmal membranes, it is suggested that the observed stimulation of exchange activity involves a local electrostatic effect of the bound cations in accelerating a rate-limiting step in the reaction mechanism for Na-Ca exchange.
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D004533:Egtazic Acid / Q000494:pharmacology; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D009861:Onium Compounds / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology*; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger
chemical_list: D002352:Carrier Proteins; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D019831:Sodium-Calcium Exchanger; D004533:Egtazic Acid; D011796:Quinacrine; D002118:Calcium; C013289:tetraphenylphosphonium