title: Attenuation by antioxidants of Na+/K+ ATPase inhibition by toxic concentrations of isoproterenol in cultured rat myocardial cells.
abstract: We have reported previously that toxic concentrations of isoproterenol caused severe alterations in the structural integrity of the sarcolemma and mitochondria found in primary cultures of rat myocardial cells [8, 9]. Mitochondrial injury was observed 1.5 h after exposure to isoproterenol, whereas leakage of intracellular ions and enzymes was observed only after prolonged exposures (greater than 4 h). Ascorbic acid and sodium bisulfite prevented the cytotoxic effects of isoproterenol in our cell culture system. Takeo et al. [13] suggested that adrenochrome (an oxidative metabolite of epinephrine) specifically inhibits the activity of the sodium/potassium ATPase. Other investigators have shown that an indole metabolite of epinephrine inhibited actomyosin ATPase [1, 4]. These inhibitory actions may result from an interaction between the oxidative metabolites and sulfhydryl groups present in the enzyme [13]. Inhibition of the sodium/potassium ATPase is associated with an increase in the intracellular concentration of Na+ and Ca2+ and a decrease in intracellular K+. Changes in the intracellular concentration of these ions are commonly seen in heart cell damage and contractile failure [2]. The present study was designed to determine if isoproterenol, a synthetic catecholamine, inhibits the sodium/potassium ATPase activity in a primary culture system of rat myocardial cells.
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D046508:Culture Techniques; D004573:Electrolytes / Q000378:metabolism; D007545:Isoproterenol / Q000633:toxicity*; D008929:Mitochondria, Heart / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013447:Sulfites / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D004573:Electrolytes; D013447:Sulfites; D000254:Sodium-Potassium-Exchanging ATPase; D007545:Isoproterenol; D001205:Ascorbic Acid; C009279:sodium bisulfite