Fk. Racke et Ef. Nemeth, STIMULUS-SECRETION COUPLING IN PARATHYROID CELLS DEFICIENT IN PROTEIN-KINASE-C ACTIVITY, The American journal of physiology, 267(3), 1994, pp. 50000429-50000438
The role of protein kinase C (PKC) in regulating cytosolic Ca2+ concen
trations ([Ca2+](i)) and parathyroid hormone (PTH) secretion was studi
ed in bovine parathyroid cells rendered deficient in PKC activity by i
ncubation with phorbol 12-myristate 13-acetate (PIMA). Pretreatment wi
th PMA caused a time- and concentration-dependent loss of functional P
KC activity as assessed by the failure of [Ca2+](i) and PTH secretion
to respond to the subsequent addition of PKC activators or the inhibit
or staurosporine. Pretreatment for 24 h with 1 mu M PMA caused a loss
of 85% of the total and 98% of the cytosolic PKC activity. Cells so pr
etreated were considered to be ''PKC downregulated.'' Increasing the c
oncentration of extracellular Ca2+ or Mg2+ caused corresponding increa
ses in [Ca2+](i) that were similar in control and in PKC-downregulated
cells. PTH secretion regulated by extracellular Ca2+ or Mg2+ was like
wise similar in control and PKC-downregulated cells. Stimulus-secretio
n coupling is thus unimpaired in parathyroid cells deficient in PKC ac
tivity. Cytosolic Ca2+ responses remained depressed in cells incubated
for 24 h with low concentrations of PMA (30 or 100 nM). However, unde
r these conditions, extracellular Ca2+ still suppressed PTH secretion
similarly to control cells. These results reveal a dissociation betwee
n cytosolic Ca2+ and PTH secretion and suggest that signals other than
cytosolic Ca2+ are involved in the regulation of PTH secretion.