Ca2+-regulated expression of aldosterone synthase is mediated by calmodulin and calmodulin-dependent protein kinases

Vincenzo Pezzi, Colin D. Clyne, Sebastiano Ando, James Michael Mathis, William E. Rainey

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

The chronic maintenance of aldosterone production in the adrenal zona glomerulosa is associated with increased expression of aldosterone synthase (P450aldo), the enzyme responsible for the conversion of 11- deoxycorticosterone to aldosterone. The major physiologic regulators of aldosterone production are angiotensin II (ANG II) and (K+) which act in part through increasing intracellular calcium ([Ca2+](i)). Recently we demonstrated that increased [Ca2+](i) is associated with K+ induction of P450aldo expression. To determine whether Ca2+ regulation of P450aldo is mediated through calmodulin or calmodulin-dependent kinases (CaMK), we investigated the actions of calmidazolium (a calmodulin inhibitor) and KN93 (an inhibitor of CaMK) on expression of P450aldo in human adrenocortical H295R cell line. Treatment with either calmidazolium or KN93 completely inhibited K+-stimulated expression of P450aldo mRNA with little effect on ANG II or dibutyryl cyclic AMP-stimulated induction of this transcript. Cellular calcium levels were also increased using the calcium ionophore ionomycin and calcium channel agonist Bay K 8644. These compounds increased P450aldo mRNA and this calcium induction was inhibited by calmidazolium and KN93. These data show that K+-stimulated expression of P450aldo mRNA is regulated in a Ca2+ sensitive manner through mechanisms involving calmodulin and CaMK.

Original languageEnglish
Pages (from-to)835-838
Number of pages4
JournalEndocrinology
Volume138
Issue number2
DOIs
StatePublished - 1 Jan 1997

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calmidazolium
Cytochrome P-450 CYP11B2
Calcium-Calmodulin-Dependent Protein Kinases
Calmodulin
Aldosterone
Zona Glomerulosa
Calcium
Angiotensin II
Messenger RNA
Calcium Channel Agonists
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Desoxycorticosterone
Bucladesine
Ionomycin
Calcium Ionophores
Maintenance
Cell Line
Enzymes

Cite this

Pezzi, Vincenzo ; Clyne, Colin D. ; Ando, Sebastiano ; Mathis, James Michael ; Rainey, William E. / Ca2+-regulated expression of aldosterone synthase is mediated by calmodulin and calmodulin-dependent protein kinases. In: Endocrinology. 1997 ; Vol. 138, No. 2. pp. 835-838.
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Ca2+-regulated expression of aldosterone synthase is mediated by calmodulin and calmodulin-dependent protein kinases. / Pezzi, Vincenzo; Clyne, Colin D.; Ando, Sebastiano; Mathis, James Michael; Rainey, William E.

In: Endocrinology, Vol. 138, No. 2, 01.01.1997, p. 835-838.

Research output: Contribution to journalArticle

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