Stimulatory action of Ba2+ on catecholamine biosynthesis in cultured bovine adrenal chromaffin cells: possible relation to protein kinase C.
The effect of Ba2+ on the catecholamine biosynthetic activity was studied by measuring the formation of [14C]catecholamines from L-[14C]tyrosine in cultured adrenal chromaffin cells. In the absence of Ca2+, [14C]catecholamine formation was markedly stimulated by Ba2+, and this stimulation was observed in a manner dependent on its concentration. The stimulation of [14C]catecholamine formation by relatively low concentrations of Ba2+ was suppressed by polymyxin B, a typical inhibitor of Ca2+/phospholipid-dependent protein kinase (protein kinase C); and this inhibitory action of polymyxin B was attenuated by increasing the Ba2+ concentration. On the other hand, a tendency toward the enhancement of Ba2+-stimulated [14C]catecholamine formation was observed by a protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA). In contrast to the acute effect of TPA, [14C]catecholamine formation stimulated by Ba2+ was reduced by long-term exposure of chromaffin cells to a high concentration of TPA, which has already been reported to cause the reduction of protein kinase C activity as a result of the down-regulation of this enzyme. These findings suggest that Ba2+ stimulates catecholamine biosynthesis, probably through its direct action on protein kinase C in adrenal chromaffin cells.
Morita
K
K
Department of Pharmacology, Tokushima University School of Medicine, Japan.
Teraoka
K
K
Azuma
M
M
Oka
M
M
Hamano
S
S
D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001464:Barium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002395:Catecholamines / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D002417:Cattle; D002478:Cells, Cultured; D002837:Chromaffin Granules / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D011112:Polymyxin B / Q000494:pharmacology; D011493:Protein Kinase C / Q000096:biosynthesis
D002395:Catecholamines; D001464:Barium; D011493:Protein Kinase C; D011112:Polymyxin B