Electron spin resonance studies on the influence of carbocromen on mitochondria and oligomycin-sensitive mitochondrial ATPase.
The action of ethyl 3-(2-diethylaminoethyl)-4-methyl-2-oxo(2H)-1-benzopyran-7-yloxyacetate (carbocromen, Intensain) on the structure of mitochondria from rat liver and bovine heart and on oligomycin-sensitive (OS)-ATPase was studied using the spin labelling method (ESR). Most prominent results were found with the spin label 4-maleimido-2,2,6,6-tetramethylpiperidinooxyl. In bovine heart mitochondria ho/h-1 ratios in repeated scans increased in presence of carbocromen (20--40 mumol/l), indicating a decrease in mobility of the spin label 100. Reduction rates of spin label were comparable in both controls and carbocromen treated samples. Carbocromen under similar conditions had no effect on rat liver mitochondria. In bovine heart mitochondrial OS-ATPase a concentration-dependent increase of mobile parts of the spectra was found. The ATPase activities indicated a substrate inhibition from concentration of about 2.85 mmol ATP onward. As a working hypothesis it is proposed that in the presence of high substrate concentrations, the drug may decrease ATPase activity, an elevation of which may have fatal consequences in myocardial ischemic disease.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D002417:Cattle; D002866:Chromonar / Q000494:pharmacology*; D003374:Coumarins / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D066298:In Vitro Techniques; D008566:Membranes / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology*; D051381:Rats
D003374:Coumarins; D009840:Oligomycins; D000251:Adenosine Triphosphatases; D002866:Chromonar