Effects of bioflavonoids on exocytotic release of catecholamines from digitonin-permeabilized chromaffin cells: A comparison with the effects of other protein kinase C inhibitors

Abstract

The effects of bioflavonoids on catecholamine release from permeabilized adrenal chromaffin cells were examined to show their intracellular actions on exocytosis. The release from these permeabilized cells in response to a direct calcium challenge was shown to be markedly inhibited by quercetin in a manner dependent on its concentration. Apigenin was also shown to cause a moderate inhibitory action, but flavone caused no significant effect on the release under the experimental conditions used here. Furthermore, the inhibitory actions of these flavonoids on the phorbol ester-dependent fraction of catecholamine release were shown to be more pronounced than those on the calcium-dependent fraction. The effects of bioflavonoids on the calcium-dependent and the phorbol ester-dependent releases were then compared with those of other protein kinase C inhibitors, and quercetin was shown to cause a potent inhibitory action on the exocytotic secretory process, which was almost equivalent to those caused by polymyxin B and neomycin. Both quercetin and apigenin were clearly shown to inhibit the phorbol ester-dependent as well as the calcium-dependent release of catecholamines from digitonin-permeabilized chromaffin cells. The inhibitory actions of these compounds were therefore thought to be attributed to their inhibitory actions on protein kinase C in the cytoplasmic space of the permeabilized cells. Thus, these results seem to provide further evidence for a possible involvement of protein kinase C as one of the sites for calcium action in the intracellular mechanism of exocytotic secretion.