Protein kinase C modulates hormone secretion regulated by extracellular polycations in bovine parathyroid cells
1. The role of protein kinase C (PKC) in the regulation of parathyroid hormone (PTH) secretion was examined in dissociated bovine parathyroid cells. 2. Increasing the concentration of extracellular Ca2+ from 0.5 to 2 mM inhibited PTH secretion by 60-80%. Similar depressive effects on secretion were...
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Veröffentlicht in: | The Journal of physiology 1993-08, Vol.468 (1), p.163-176 |
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Zusammenfassung: | 1. The role of protein kinase C (PKC) in the regulation of parathyroid hormone (PTH) secretion was examined in dissociated
bovine parathyroid cells. 2. Increasing the concentration of extracellular Ca2+ from 0.5 to 2 mM inhibited PTH secretion by
60-80%. Similar depressive effects on secretion were obtained by increasing the concentration of extracellular Mg2+ from 1
to 7 mM or by adding La3+ (to 40 microM). The PKC activator phorbol myristate acetate (PMA) depressed PTH secretion at the
lower and potentiated secretion at the higher concentrations of extracellular Ca2+, Mg2+ or La3+. The inhibitory effect of
PKC on secretion correlated positively with the magnitude of the inhibitory effect elicited by elevated extracellular Ca2+.
3. The stimulatory effects of PKC activators on PTH secretion were reversed completely and the inhibitory 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 secretion at intermediate concentrations (around 1 mM) of extracellular
Ca2+. 4. The stimulatory effects of PKC activators on secretion were overcome by increases in the concentration of extracellular
Ca2+ (to 5 or 10 mM) or La3+ (to 100 microM). In contrast, increasing the concentration of extracellular Mg2+ to 11 or 19
mM did not alleviate the potentiating effects of PKC activators. The different results obtained with Ca2+ and 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 isoprenaline was not affected by PKC activators or staurosporine. Similarly, the inhibitory effects of extracellular ATP
gamma S on secretion were unaffected 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 inhibitory
effects on [Ca2+]i and inositol trisphosphate formation, showing that PKC blunts the mechanisms associated with extracellular
Ca(2+)-induced inhibition of secretion. The specificity of these actions suggests that PKC acts at a very early step of stimulus-secretion
coupling in parathyroid cells, specific to that used by extracellular polycations and perhaps involving the Ca2+ rece |
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ISSN: | 0022-3751 1469-7793 |
DOI: | 10.1113/jphysiol.1993.sp019765 |