The effects of protein kinase-C agonists on parathyroid hormone release and intracellular free Ca2+ in bovine parathyroid cells.

High extracellular Ca2+ stimulates the accumulation of inositol trisphosphate and diacylglycerol in parathyroid cells and suppresses PTH release. Since diacylglycerol is an endogenous activator of protein kinase-C, these observations would suggest that activation of protein kinase-C is associated with inhibition of PTH release. However, phorbol esters, which stimulate protein kinase-C activity, have been reported to enhance PTH release. To clarify the role of protein kinase-C in the regulation of PTH secretion, we studied the responses of parathyroid cells to phorbol myristate acetate (PMA), bryostatin- 1, and 1,2-dioctanoylglycerol (diC8). PMA and bryostatin-1 translocated protein kinase-C activity from the soluble to particulate fractions of cell homogenates. Phosphotransferase activity in the particulate fractions increased from 21 ± 4% to 93 ± 6% of the total activity after 10 min of exposure to PMA (10-6 M) and from 21 ± 2% to 69 ± 2% after 5 min of exposure to bryostatin-l (10-7 M). These three stru...