INVOLVEMENT OF MONOAMINE-OXIDASE AND NORADRENALINE UPTAKE IN THE POSITIVE CHRONOTROPIC EFFECTS OF APIGENIN IN RAT ATRIA

In rat isolated atria spontaneously beating and labelled with [H-3]nor adrenaline, exposure to the flavonoid apigenin increased the atrial ra te in a concentration-dependent manner (0.01-30 mu M). This increase w as accompanied by a reduction of 60% in the uptake of [H-3]noradrenali ne as well as by a modification in the pattern of [H-3]noradrenaline a nd metabolites spontaneously released. Sixty minutes after exposure to 30 mu M apigenin, the proportion of unmetabolized [H-3]noradrenaline increased from 11% to 45% of the total products bath whereas the triti ated O-methylated deaminated metabolites decreased from 33% to 14% of the total efflux. A small but significant decrease in the outflow of [ H-3]3,4-dihydroxymandelic acid as well as a tendency to a decrease in the efflux of [H-3]3,4-dihydroxyphenylglycol was also observed. Furthe rmore, apigenin inhibited in a concentration-dependent manner the acti vity of monoamine oxidase in the rat atrial homogenates. The calculate d IC50 (7.7 mu M) was within the range that produced 50% of the maxima l increase in atrial rate. It is concluded that apigenin possesses the property to increase the atrial rate, probably as a result of a reduc tion in noradrenaline uptake as well as in monoamine oxidase activity.