Stimulation of parathyroid hormone secretion by phorbol esters is associated with a decrease of cytosolic calcium

Unlike in other endocrine systems calcium inhibits parathyroid hormone (PTH) secretion and this inhibition is paralleled by a rise of cytosolic calcium concentration ([Ca]i). Because of evidence that diglyceride levels and protein kinase C activity are also decreased by high extracellular calcium we have investigated the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, on [Ca]i and PTH secretion using dispersed bovine parathyroid cells. At 1.5 mM medium calcium TPA enhanced PTH secretion and caused reduction of [Ca]i from 639 +/- 36 nM (SE) to 335 +/- 21 nM (P less than 0.001); at 0.5 mM calcium TPA was ineffective. Moreover, TPA suppressed the rise of [Ca]i evoked by high extracellular calcium. Thus TPA presumably stimulates PTH secretion via activation of protein kinase C, and the lowering of [Ca]i may TPA presumably stimulates PTH secretion via activation of protein kinase C, and the lowering of [Ca]i may be a secondary event related to diglyceride availability.