Effects of phorbol ester on catecholamine secretion and protein phosphorylation in adrenal medullary cell cultures.

Publisher Website
Google Scholar
Abstract
The effects of phorbol 12-myristate 13-acetate (PMA) on catecholamine secretion and protein phosphorylation from intact and digitonin-treated [bovine] chromaffin cells were investigated. PMA (10-300 nM), an activator of protein kinase C, caused a slow Ca2+-dependent release of catecholamine from intact chromaffin cells that was potentiated by the Ca2+ ionophore ionomycin. PMA also enhanced secretion induced by Ba2+. In cells with plasma membranes rendered permeable by digitonin to Ca2+, ATP and protein, PMA (100 nM) enhanced Ca2+-dependent secretion .apprxeq. 70% at 0.5 .mu.M Ca2+ and 30% at 10 .mu.M Ca2+. PMA enhanced the maximal response to Ca2+ .apprxeq. 25% and decreased the Ca2+ concentration required for half-maximal secretion .apprxeq. 30%. The effects of PMA on chromaffin cells were associated with a 2- to 3-fold increase in the phosphorylation of a 56-kDa [kilodalton] protein that may be tyrosine hydroxylase. Other proteins were phosphorylated to a lesser extent. PMA may increase protein kinase activity and secretion in chromaffin cells and raise the possibility that protein kinase C modulates catecholamine secretion in chromaffin cells.