Characterization of NADPH-cytochrome P-450 reductase in a mouse hepatoma cell line

NADPH-cytochrome c reductase in Hepa-1 cells was induced 2-fold by phenobarbital, but was not induced by benz[a]anthracene or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The apparent K_m of the enzyme for NADPH was 0.57 μM; the activity was inhibitable by NADP; and segregated primarily to the microsomal fraction. Cytoplasm of Hepa-1 cells bound antibody to rabbit cytochrome P-450 reductase. 3T3 cells, which possessed one sixth of the cytochrome c reductase activity of Hepa-1 cells, bound correspondingly less cytochrome P-450 reductase antibody. This supports the notion that cytochrome P-450 reductase was responsible for the cytochrome c reductase activity that was measured.     

The role of free fatty acids in the production of ventricular arrhythmias after acute coronary artery occlusion

After After coronary artery occlusion had been produced in intact dogs, marked elevation of plasma FFA was usually associated with the development of frequent ventricular ectopic systoles and sometimes with ventricular tachycardia or even ventricular fibrillation. These arrhythmias occurred 10–30 min. after the maximum recorded level of FFA.— Elevation of plasma FFA was achieved by inducing plasma lipolysis with heparin. The increased frequency of ventricular ectopic systoles could be reduced and ventricular tachycardia abolished by the administration of protamine sulphate, which has no known anti-arrhythmic effect on spontaneous arrhythmia, but suppresses heparin-induced plasma lipolysis.— No haemodynamic changes occurred with the administration of heparin and Intralipid. While infusion of Intralipid and heparin caused reduction in pH of approximately 0.04, evidence is presented that this is not a stimulus for increased arrhythmia.—The administration of noradrenaline to dogs with coronary artery occlusion can also cause arrhythmia even when administered in extremely small doses. The effect is a biphasic one. An immediate initial arrhythmia may occur and is associated with a rise in blood pressure and a reflex bradycardia but not with any significant elevation of FFA. Such arrhythmias disappear when sinus bradycardia is prevented. Arrhythmia can recur during the infusion of nor-adrenaline in the absence of haemodynamie change and this is associated with marked elevation of plasma FFA. This late arrhythmia can be suppressed or prevented by the administration of a drug which reduces adipose tissue lipolysis.—It is concluded that elevated plasma FFA can have an ar-rhythmogenic action when there is associated myocardial hypoxia and this effect can be independent of catecholamine activity.