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

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.