Abstract
The purpose of this study was to evaluate regulation of PTH secretion by protein kinase-C (PKC) in adult bovine parathyroid cells. Extracellular calcium (Ca2+ e) is the main physiological regulator of PTH secretion. Putative second messengers include intracellular calcium (Ca2+ i), cAMP, inositol trisphosphate, and diacylglycerol (DAG). Both DAG and Ca2+ i activate PKC. Certain phorbol esters mimic the effect of DAG and cause prolonged stimulation of PKC. The stimulatory phorbol esters 12-0-tetradecanoylphorbol acetate (1 µM) and phorbol-12, 13-dibutyrate (1 µM) did not affect PTH secretion at low Ca2+ e, but increased both individual cell secretion and recruitment of cells to secrete at high Ca2+ e. The PKC inhibitors H7 (1 µM), tamoxifen (10 µm), and sphinganine (5 µm) inhibited PTH release at low Ca2+ e(0.1 and 0.2 mM) and decreased cell recruitment over the physiological range of Ca2+ e- The nonstimulatory phorbol esters 4α-phorbol-12, 13-didecanoate (1 µM) and phorbol-13-monoacetate (1 µM) had no effect on PTH secretion. To assess the mechanism by which certain phorbol esters stimulated PTH secretion, in situ hybridization for PTH mRNA was performed. Phorbol-12, 13-dibutyrate (1 µM) qualitatively increased steady state PTH mRNA levels compared to control values. We conclude that 1) PKC stimulation increased PTH secretion at high Ca2+ e, but not at low Ca2+ e; 2) PKC inhibition decreased PTH secretion at low Ca2+ e; and 3) PKC stimulation increased steady state PTH mRNA levels. These data suggest that PKC plays an important regulatory role in the synthesis and secretion of PTH.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1168-1175 |
| Number of pages | 8 |
| Journal | Endocrinology |
| Volume | 132 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jan 1 1993 |
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- Endocrinology
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Regulation of parathyroid hormone release by protein kinase-C is dependent on extracellular calcium in bovine parathyroid cells. / Clarke, Bart; Hassager, Christian; Fitzpatrick, Lorraine A.
In: Endocrinology, Vol. 132, No. 3, 01.01.1993, p. 1168-1175.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regulation of parathyroid hormone release by protein kinase-C is dependent on extracellular calcium in bovine parathyroid cells
AU - Clarke, Bart
AU - Hassager, Christian
AU - Fitzpatrick, Lorraine A.
PY - 1993/1/1
Y1 - 1993/1/1
N2 - The purpose of this study was to evaluate regulation of PTH secretion by protein kinase-C (PKC) in adult bovine parathyroid cells. Extracellular calcium (Ca2+ e) is the main physiological regulator of PTH secretion. Putative second messengers include intracellular calcium (Ca2+ i), cAMP, inositol trisphosphate, and diacylglycerol (DAG). Both DAG and Ca2+ i activate PKC. Certain phorbol esters mimic the effect of DAG and cause prolonged stimulation of PKC. The stimulatory phorbol esters 12-0-tetradecanoylphorbol acetate (1 µM) and phorbol-12, 13-dibutyrate (1 µM) did not affect PTH secretion at low Ca2+ e, but increased both individual cell secretion and recruitment of cells to secrete at high Ca2+ e. The PKC inhibitors H7 (1 µM), tamoxifen (10 µm), and sphinganine (5 µm) inhibited PTH release at low Ca2+ e(0.1 and 0.2 mM) and decreased cell recruitment over the physiological range of Ca2+ e- The nonstimulatory phorbol esters 4α-phorbol-12, 13-didecanoate (1 µM) and phorbol-13-monoacetate (1 µM) had no effect on PTH secretion. To assess the mechanism by which certain phorbol esters stimulated PTH secretion, in situ hybridization for PTH mRNA was performed. Phorbol-12, 13-dibutyrate (1 µM) qualitatively increased steady state PTH mRNA levels compared to control values. We conclude that 1) PKC stimulation increased PTH secretion at high Ca2+ e, but not at low Ca2+ e; 2) PKC inhibition decreased PTH secretion at low Ca2+ e; and 3) PKC stimulation increased steady state PTH mRNA levels. These data suggest that PKC plays an important regulatory role in the synthesis and secretion of PTH.
AB - The purpose of this study was to evaluate regulation of PTH secretion by protein kinase-C (PKC) in adult bovine parathyroid cells. Extracellular calcium (Ca2+ e) is the main physiological regulator of PTH secretion. Putative second messengers include intracellular calcium (Ca2+ i), cAMP, inositol trisphosphate, and diacylglycerol (DAG). Both DAG and Ca2+ i activate PKC. Certain phorbol esters mimic the effect of DAG and cause prolonged stimulation of PKC. The stimulatory phorbol esters 12-0-tetradecanoylphorbol acetate (1 µM) and phorbol-12, 13-dibutyrate (1 µM) did not affect PTH secretion at low Ca2+ e, but increased both individual cell secretion and recruitment of cells to secrete at high Ca2+ e. The PKC inhibitors H7 (1 µM), tamoxifen (10 µm), and sphinganine (5 µm) inhibited PTH release at low Ca2+ e(0.1 and 0.2 mM) and decreased cell recruitment over the physiological range of Ca2+ e- The nonstimulatory phorbol esters 4α-phorbol-12, 13-didecanoate (1 µM) and phorbol-13-monoacetate (1 µM) had no effect on PTH secretion. To assess the mechanism by which certain phorbol esters stimulated PTH secretion, in situ hybridization for PTH mRNA was performed. Phorbol-12, 13-dibutyrate (1 µM) qualitatively increased steady state PTH mRNA levels compared to control values. We conclude that 1) PKC stimulation increased PTH secretion at high Ca2+ e, but not at low Ca2+ e; 2) PKC inhibition decreased PTH secretion at low Ca2+ e; and 3) PKC stimulation increased steady state PTH mRNA levels. These data suggest that PKC plays an important regulatory role in the synthesis and secretion of PTH.
UR - http://www.scopus.com/inward/record.url?scp=0027528519&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027528519&partnerID=8YFLogxK
U2 - 10.1210/endo.132.3.8440177
DO - 10.1210/endo.132.3.8440177
M3 - Article
C2 - 8440177
AN - SCOPUS:0027528519
VL - 132
SP - 1168
EP - 1175
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 3
ER -