The role of protein kinase-C in control of aldosterone production by rat adrenal glomerulosa cells

Activation of protein kinase-C by stimulation with potassium

György Hajnóczky, P. Várnai, L. Buday, A. Faragó, A. Spät

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Abstract

The role of protein kinase-C (PKC) in control of the function of rat adrenal glomerulosa cells was studied. Phorbol 12-myristate 13-acetate (PMA), an activator of PKC, inhibited the stimulation of aldosterone production induced by K+ (5.4 mM) or ACTH (5 pM) in a dose-dependent manner. Phorbol 12,13-dibutyrate, another phorbol ester that activates PKC, also exerted an inhibitory effect, while the inactive 4α-phorbol 12,13-didecanoate failed to affect aldosterone production. The inhibitory effect of PMA (5 nM) was reversed by preincubation of the cells with staurosporine (ST; 50 nM), an inhibitor of PKC. These data suggest that pharmacological activation of PKC initiates an inhibitory mechanism in rat glomerulosa cells. To elucidate whether PKC is activated by physiological stimuli, the effects of ST and down-regulation of PKC by prolonged pretreatment with PMA on stimulation of aldosterone production were studied. The effects of angiotensin-II (All) and K+, but not that of ACTH, were enhanced by ST pretreatment. This potentiation was prompt and transient in the case of AII (2.5 nM), while it developed gradually when the cells were stimulated with K+ (5.4 or 18 mM). Long term pretreatment (6 h) of glomerulosa cells with PMA also enhanced the stimulatory effect of AII (300 pM) and K+ (5.4 mM). These data together suggest that the actions of AII and K+ on aldosterone production involve a PKC-mediated inhibition. Activation of PKC by AII is probably due to formation of diacylglycerol via receptor-mediated activation of phosphoinositide-specific phospholipase-C. Stimulation with K+ caused a moderate accumulation of [3H]inositol phosphate in a concentration-dependent manner. Since this effect was abolished by nifedipine, activation of phospholipase-C may have been secondary to Ca2+ entry. The concomitant formation of diacylglycerol may contribute to activation of PKC in K+ stimulated cells. In conclusion, our data support the view that PKC participates in the physiological control of aldosterone production by rat adrenal glomerulosa cells. In addition to All, K+ may activate PKC. Regardless of whether the enzyme is activated by phorbol esters or physiological stimuli, it exerts an inhibitory, rather than stimulatory, action on steroid production.

Original languageEnglish
Pages (from-to)2230-2236
Number of pages7
JournalEndocrinology
Volume130
Issue number4
Publication statusPublished - Apr 1992

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Zona Glomerulosa
Aldosterone
Protein Kinase C
Potassium
Acetates
Diglycerides
Phorbol Esters
Adrenocorticotropic Hormone
Phorbol 12,13-Dibutyrate
Phosphoinositide Phospholipase C
Inositol Phosphates
Staurosporine
Type C Phospholipases
Nifedipine
Angiotensin II

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

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title = "The role of protein kinase-C in control of aldosterone production by rat adrenal glomerulosa cells: Activation of protein kinase-C by stimulation with potassium",
abstract = "The role of protein kinase-C (PKC) in control of the function of rat adrenal glomerulosa cells was studied. Phorbol 12-myristate 13-acetate (PMA), an activator of PKC, inhibited the stimulation of aldosterone production induced by K+ (5.4 mM) or ACTH (5 pM) in a dose-dependent manner. Phorbol 12,13-dibutyrate, another phorbol ester that activates PKC, also exerted an inhibitory effect, while the inactive 4α-phorbol 12,13-didecanoate failed to affect aldosterone production. The inhibitory effect of PMA (5 nM) was reversed by preincubation of the cells with staurosporine (ST; 50 nM), an inhibitor of PKC. These data suggest that pharmacological activation of PKC initiates an inhibitory mechanism in rat glomerulosa cells. To elucidate whether PKC is activated by physiological stimuli, the effects of ST and down-regulation of PKC by prolonged pretreatment with PMA on stimulation of aldosterone production were studied. The effects of angiotensin-II (All) and K+, but not that of ACTH, were enhanced by ST pretreatment. This potentiation was prompt and transient in the case of AII (2.5 nM), while it developed gradually when the cells were stimulated with K+ (5.4 or 18 mM). Long term pretreatment (6 h) of glomerulosa cells with PMA also enhanced the stimulatory effect of AII (300 pM) and K+ (5.4 mM). These data together suggest that the actions of AII and K+ on aldosterone production involve a PKC-mediated inhibition. Activation of PKC by AII is probably due to formation of diacylglycerol via receptor-mediated activation of phosphoinositide-specific phospholipase-C. Stimulation with K+ caused a moderate accumulation of [3H]inositol phosphate in a concentration-dependent manner. Since this effect was abolished by nifedipine, activation of phospholipase-C may have been secondary to Ca2+ entry. The concomitant formation of diacylglycerol may contribute to activation of PKC in K+ stimulated cells. In conclusion, our data support the view that PKC participates in the physiological control of aldosterone production by rat adrenal glomerulosa cells. In addition to All, K+ may activate PKC. Regardless of whether the enzyme is activated by phorbol esters or physiological stimuli, it exerts an inhibitory, rather than stimulatory, action on steroid production.",
author = "Gy{\"o}rgy Hajn{\'o}czky and P. V{\'a}rnai and L. Buday and A. Farag{\'o} and A. Sp{\"a}t",
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TY - JOUR

T1 - The role of protein kinase-C in control of aldosterone production by rat adrenal glomerulosa cells

T2 - Activation of protein kinase-C by stimulation with potassium

AU - Hajnóczky, György

AU - Várnai, P.

AU - Buday, L.

AU - Faragó, A.

AU - Spät, A.

PY - 1992/4

Y1 - 1992/4

N2 - The role of protein kinase-C (PKC) in control of the function of rat adrenal glomerulosa cells was studied. Phorbol 12-myristate 13-acetate (PMA), an activator of PKC, inhibited the stimulation of aldosterone production induced by K+ (5.4 mM) or ACTH (5 pM) in a dose-dependent manner. Phorbol 12,13-dibutyrate, another phorbol ester that activates PKC, also exerted an inhibitory effect, while the inactive 4α-phorbol 12,13-didecanoate failed to affect aldosterone production. The inhibitory effect of PMA (5 nM) was reversed by preincubation of the cells with staurosporine (ST; 50 nM), an inhibitor of PKC. These data suggest that pharmacological activation of PKC initiates an inhibitory mechanism in rat glomerulosa cells. To elucidate whether PKC is activated by physiological stimuli, the effects of ST and down-regulation of PKC by prolonged pretreatment with PMA on stimulation of aldosterone production were studied. The effects of angiotensin-II (All) and K+, but not that of ACTH, were enhanced by ST pretreatment. This potentiation was prompt and transient in the case of AII (2.5 nM), while it developed gradually when the cells were stimulated with K+ (5.4 or 18 mM). Long term pretreatment (6 h) of glomerulosa cells with PMA also enhanced the stimulatory effect of AII (300 pM) and K+ (5.4 mM). These data together suggest that the actions of AII and K+ on aldosterone production involve a PKC-mediated inhibition. Activation of PKC by AII is probably due to formation of diacylglycerol via receptor-mediated activation of phosphoinositide-specific phospholipase-C. Stimulation with K+ caused a moderate accumulation of [3H]inositol phosphate in a concentration-dependent manner. Since this effect was abolished by nifedipine, activation of phospholipase-C may have been secondary to Ca2+ entry. The concomitant formation of diacylglycerol may contribute to activation of PKC in K+ stimulated cells. In conclusion, our data support the view that PKC participates in the physiological control of aldosterone production by rat adrenal glomerulosa cells. In addition to All, K+ may activate PKC. Regardless of whether the enzyme is activated by phorbol esters or physiological stimuli, it exerts an inhibitory, rather than stimulatory, action on steroid production.

AB - The role of protein kinase-C (PKC) in control of the function of rat adrenal glomerulosa cells was studied. Phorbol 12-myristate 13-acetate (PMA), an activator of PKC, inhibited the stimulation of aldosterone production induced by K+ (5.4 mM) or ACTH (5 pM) in a dose-dependent manner. Phorbol 12,13-dibutyrate, another phorbol ester that activates PKC, also exerted an inhibitory effect, while the inactive 4α-phorbol 12,13-didecanoate failed to affect aldosterone production. The inhibitory effect of PMA (5 nM) was reversed by preincubation of the cells with staurosporine (ST; 50 nM), an inhibitor of PKC. These data suggest that pharmacological activation of PKC initiates an inhibitory mechanism in rat glomerulosa cells. To elucidate whether PKC is activated by physiological stimuli, the effects of ST and down-regulation of PKC by prolonged pretreatment with PMA on stimulation of aldosterone production were studied. The effects of angiotensin-II (All) and K+, but not that of ACTH, were enhanced by ST pretreatment. This potentiation was prompt and transient in the case of AII (2.5 nM), while it developed gradually when the cells were stimulated with K+ (5.4 or 18 mM). Long term pretreatment (6 h) of glomerulosa cells with PMA also enhanced the stimulatory effect of AII (300 pM) and K+ (5.4 mM). These data together suggest that the actions of AII and K+ on aldosterone production involve a PKC-mediated inhibition. Activation of PKC by AII is probably due to formation of diacylglycerol via receptor-mediated activation of phosphoinositide-specific phospholipase-C. Stimulation with K+ caused a moderate accumulation of [3H]inositol phosphate in a concentration-dependent manner. Since this effect was abolished by nifedipine, activation of phospholipase-C may have been secondary to Ca2+ entry. The concomitant formation of diacylglycerol may contribute to activation of PKC in K+ stimulated cells. In conclusion, our data support the view that PKC participates in the physiological control of aldosterone production by rat adrenal glomerulosa cells. In addition to All, K+ may activate PKC. Regardless of whether the enzyme is activated by phorbol esters or physiological stimuli, it exerts an inhibitory, rather than stimulatory, action on steroid production.

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