scholarly journals Role of tyrosine kinase and protein kinase C in the steroidogenic actions of angiotensin II, α-melanocyte-stimulating hormone and corticotropin in the rat adrenal cortex

1995 ◽  
Vol 305 (2) ◽  
pp. 433-438 ◽  
Author(s):  
S Kapas ◽  
A Purbrick ◽  
J P Hinson
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Zona Glomerulosa ◽  
Aldosterone Secretion ◽  
Melanocyte Stimulating Hormone ◽  
Kinase C ◽  
Stimulating Hormone

The role of protein kinases in the steroidogenic actions of alpha-melanocyte-stimulating hormone (alpha-MSH), angiotensin II (AngII) and corticotropin (ACTH) in the rat adrenal zona glomerulosa was examined. Ro31-8220, a potent selective inhibitor of protein kinase C (PKC), inhibited both AngII- and alpha-MSH-stimulated aldosterone secretion but had no effect on aldosterone secretion in response to ACTH. The effect of Ro31-8220 on PKC activity was measured in subcellular fractions. Basal PKC activity was higher in cytosol than in membrane or nuclear fractions. Incubation of the zona glomerulosa with either alpha-MSH or AngII resulted in significant increases in PKC activity in the nuclear and cytosolic fractions and decreases in the membrane fraction. These effects were all inhibited by Ro31-8220. ACTH caused a significant increase in nuclear PKC activity only, and this was inhibited by Ro31-8220 without any significant effect on the steroidogenic response to ACTH, suggesting that PKC translocation in response to ACTH may be involved in another aspect of adrenal cellular function. Tyrosine phosphorylation has not previously been considered to be an important component of the response of adrenocortical cells to peptide hormones. Both AngII and alpha-MSH were found to activate tyrosine kinase, but ACTH had no effect, observations that have not been previously reported. Tyrphostin 23, a specific antagonist of tyrosine kinases, inhibited aldosterone secretion in response to AngII and alpha-MSH, but not ACTH. These data confirm the importance of PKC in the adrenocortical response to AngII and alpha-MSH, and, furthermore, indicate that tyrosine kinase may play a critical role in the steroidogenic actions of AngII and alpha-MSH in the rat adrenal zona glomerulosa.

scholarly journals Rate of calcium entry determines the rapid changes in protein kinase C activity in angiotensin II-stimulated adrenal glomerulosa cells

1994 ◽  
Vol 297 (3) ◽  
pp. 523-528 ◽  
Author(s):  
I Kojima ◽  
N Kawamura ◽  
H Shibata
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Specific Substrate ◽  
Ang Ii ◽  
Kinase C ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Peptide Phosphorylation

The present study was conducted to monitor precisely the activity of protein kinase C (PKC) in adrenal glomerulosa cells stimulated by angiotensin II (ANG II). PKC activity in cells was monitored by measuring phosphorylation of a synthetic KRTLRR peptide, a specific substrate for PKC, immediately after the permeabilization of the cells with digitonin [Heasley and Johnson J. Biol. Chem. (1989) 264, 8646-8652]. Addition of 1 nM ANG II induced a gradual increase in KRTLRR peptide phosphorylation, which reached a peak at 30 min, and phosphorylation was sustained thereafter. When the action of ANG II was terminated by adding [Sar1,Ala8]ANG II, a competitive antagonist, both Ca2+ entry and KRTLRR phosphorylation ceased rapidly, whereas diacylglyercol (DAG) content was not changed significantly within 10 min. Similarly, when blockade of Ca2+ entry was achieved by decreasing extracellular Ca2+ to 1 microM or by adding 1 microM nitrendipine, KRTLRR peptide phosphorylation was decreased within 5 min. In addition, restoration of Ca2+ entry was accompanied by an immediate increase in KRTLRR peptide phosphorylation. Under the same condition, DAG content did not change significantly. We then examined the role of the PKC pathway in ANG II-induced aldosterone production. Ro 31-8220 inhibited ANG II-induced KRTLRR phosphorylation without affecting the activity of calmodulin-dependent protein kinase II. In the presence of Ro 31-8220, ANG II-mediated aldosterone production was decreased to approx. 50%. Likewise, intracellular administration of PKC19-36, a sequence corresponding to residues 19-36 of the regulatory domain of PKC known to inhibit PKC activity, attenuated ANG II-mediated activation of PKC and aldosterone output. These results indicate a critical role of Ca2+ entry in the regulation of PKC activity by ANG II.

α-Melanocyte Stimulating Hormone-Induced Pigmentation Is Blocked by Depletion of Protein Kinase C

1996 ◽  
Vol 227 (1) ◽  
pp. 70-79 ◽  
Author(s):  
Hee-Young Park ◽  
Vladimir Russakovsky ◽  
Yi Ao ◽  
Esther Fernandez ◽  
Barbara A. Gilchrest
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Melanocyte Stimulating Hormone ◽  
Kinase C ◽  
Stimulating Hormone

scholarly journals Calcium- and Protein Kinase C–Dependent Activation of the Tyrosine Kinase PYK2 by Angiotensin II in Vascular Smooth Muscle

1998 ◽  
Vol 83 (8) ◽  
pp. 841-851 ◽  
Author(s):  
Abdelkarim Sabri ◽  
Geetha Govindarajan ◽  
Tina M. Griffin ◽  
Kenneth L. Byron ◽  
Allen M. Samarel ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Vascular Smooth Muscle ◽  
Tyrosine Kinase ◽  
Kinase C

scholarly journals Mechanism of inhibitory action of TMB-8 [8-(NN-diethylamino)octyl-3,4,5-trimethoxybenzoate] on aldosterone secretion in adrenal glomerulosa cells

1985 ◽  
Vol 232 (1) ◽  
pp. 87-92 ◽  
Author(s):  
I Kojima ◽  
K Kojima ◽  
H Rasmussen
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Calcium Release ◽  
Calcium Influx ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Aldosterone Secretion ◽  
Kinase C ◽  
Glomerulosa Cells

The mechanism of 8-(NN-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) action was evaluated in isolated adrenal glomerulosa cells. TMB-8 inhibits both angiotensin II- and K+-stimulated aldosterone secretion in a dose-dependent manner. The ID50 for angiotensin II- and K+-stimulated aldosterone secretion is 46 and 28 microM, respectively. In spite of the fact that 100 microM-TMB-8 inhibits angiotensin II-stimulated aldosterone secretion almost completely, TMB-8 (100 microM) does not inhibit angiotensin II-induced 45Ca2+ efflux from prelabelled cells nor does it affect inositol 1,4,5-trisphosphate-induced calcium release from non-mitochondrial pool(s) in saponin-permeabilized cells. TMB-8 has no inhibitory effect on A23187-induced aldosterone secretion, but 12-O-tetradecanoylphorbol 13-acetate-induced aldosterone secretion is completely abolished. TMB-8 effectively inhibits both angiotensin II- and K+-induced increases in calcium influx but has no effect on A23187-induced calcium influx. TMB-8 inhibits the activity of protein kinase C dose-dependently. These results indicate that TMB-8 inhibits aldosterone secretion without inhibiting mobilization of calcium from an intracellular pool. The inhibitory effect of TMB-8 is due largely to an inhibition of plasma membrane calcium influx, but this drug also inhibits the activity of protein kinase C directly.

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