Fk. Racke et Ef. Nemeth, PROTEIN-KINASE-C MODULATES HORMONE-SECRETION REGULATED BY EXTRACELLULAR POLYCATIONS IN BOVINE PARATHYROID CELLS, Journal of physiology, 468, 1993, pp. 163-176
1. The role of protein kinase C (PKC) in the regulation of parathyroid
hormone (PTH) secretion was examined in dissociated bovine parathyroi
d cells. 2. Increasing the concentration of extracellular Ca2+ from 0.
5 to 2 mm inhibited PTH secretion by 60-80 %. Similar depressive effec
ts on secretion were obtained by increasing the concentration of extra
cellular Mg2+ from 1 to 7 mm or by adding La3+ (to 40 mum). The PKC ac
tivator phorbol myristate acetate (PMA) depressed PTH secretion at the
lower and potentiated secretion at the higher concentrations of extra
cellular Ca2+, Mg2+ or La+. The inhibitory effect of PKC on secretion
correlated positively with the magnitude of the inhibitory effect elic
ited by elevated extracellular Ca2+. 3. The stimulatory effects of PKC
activators on PTH secretion were reversed completely and the inhibito
ry effects were reversed partially by the PKC inhibitor staurosporine.
Staurosporine alone did not affect secretion at low (0.5 mm) or high
(2 mm) concentrations of extracellular Ca2+ but it did depress secreti
on at intermediate concentrations (around 1 mm) of extracellular Ca2+.
4. The stimulatory effects of PKC activators on secretion were overco
me by increases in the concentration of extracellular Ca2+ (to 5 or 10
mm) or La3+ (to 100 muM). In contrast, increasing the concentration o
f extracellular Mg2+ to 11 or 19 mm did not alleviate the potentiating
effects of PKC activators. The different results obtained with Ca2+ a
nd Mg2+ could not be explained by their different effects on cytosolic
Ca2+ and suggests that different cations can have varying degrees of
efficacy to activate functional responses linked to the Ca2+ receptor
on bovine parathyroid cells. 5. PTH secretion stimulated by isoprenali
ne was not affected by PKC activators or staurosporine. Similarly, the
inhibitory effects of extracellular ATPgammaS on secretion were unaff
ected by PKC activators. These results show that PKC activators affect
specifically PTH secretion regulated by extracellular polycations. 6.
The stimulatory effect of PKC activators on secretion parallels its i
nhibitory effects on [Ca2+]i and inositol trisphosphate formation, sho
wing that PKC blunts the mechanisms associated with extracellular Ca2-induced inhibition of secretion. The specificity of these actions sug
gests that PKC acts at a very early step of stimulus-secretion couplin
g in parathyroid cells, specific to that used by extracellular polycat
ions and perhaps involving the Ca2+ receptor.