Regulation of aldosterone secretion by Ca v 1.3

Catherine B. Xie, Lalarukh Haris Shaikh, Sumedha Garg, Gizem Tanriver, Ada E D Teo, Junhua Zhou, Carmela Maniero, Wanfeng Zhao, Soosung Kang, Richard B. Silverman, Azizan Elena Aisha, Morris J. Brown

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Aldosterone-producing adenomas (APAs) vary in phenotype and genotype. Zona glomerulosa (ZG)-like APAs frequently have mutations of an L-type calcium channel (LTCC) Ca V 1.3. Using a novel antagonist of Ca V 1.3, compound 8, we investigated the role of Ca V 1.3 on steroidogenesis in the human adrenocortical cell line, H295R, and in primary human adrenal cells. This investigational drug was compared with the common antihypertensive drug nifedipine, which has 4.5-fold selectivity for the vascular LTCC, Ca V 1.2, over Ca V 1.3. In H295R cells transfected with wild-type or mutant Ca V 1.3 channels, the latter produced more aldosterone than wild-type, which was ameliorated by 100 1/4M of compound 8. In primary adrenal and non-transfected H295R cells, compound 8 decreased aldosterone production similar to high concentration of nifedipine (100 1/4M). Selective Ca V 1.3 blockade may offer a novel way of treating primary hyperaldosteronism, which avoids the vascular side effects of Ca V 1.2-blockade, and provides targeted treatment for ZG-like APAs with mutations of Ca V 1.3.

Original languageEnglish
Article number24697
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 21 Apr 2016

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Aldosterone
Adenoma
Zona Glomerulosa
L-Type Calcium Channels
Nifedipine
Blood Vessels
Investigational Drugs
Mutation
Hyperaldosteronism
Antihypertensive Agents
Genotype
Phenotype
Cell Line

ASJC Scopus subject areas

  • General

Cite this

Xie, C. B., Haris Shaikh, L., Garg, S., Tanriver, G., Teo, A. E. D., Zhou, J., ... Brown, M. J. (2016). Regulation of aldosterone secretion by Ca v 1.3. Scientific Reports, 6, [24697]. https://doi.org/10.1038/srep24697

Regulation of aldosterone secretion by Ca v 1.3. / Xie, Catherine B.; Haris Shaikh, Lalarukh; Garg, Sumedha; Tanriver, Gizem; Teo, Ada E D; Zhou, Junhua; Maniero, Carmela; Zhao, Wanfeng; Kang, Soosung; Silverman, Richard B.; Elena Aisha, Azizan; Brown, Morris J.

In: Scientific Reports, Vol. 6, 24697, 21.04.2016.

Research output: Contribution to journalArticle

Xie, CB, Haris Shaikh, L, Garg, S, Tanriver, G, Teo, AED, Zhou, J, Maniero, C, Zhao, W, Kang, S, Silverman, RB, Elena Aisha, A & Brown, MJ 2016, 'Regulation of aldosterone secretion by Ca v 1.3', Scientific Reports, vol. 6, 24697. https://doi.org/10.1038/srep24697
Xie CB, Haris Shaikh L, Garg S, Tanriver G, Teo AED, Zhou J et al. Regulation of aldosterone secretion by Ca v 1.3. Scientific Reports. 2016 Apr 21;6. 24697. https://doi.org/10.1038/srep24697
Xie, Catherine B. ; Haris Shaikh, Lalarukh ; Garg, Sumedha ; Tanriver, Gizem ; Teo, Ada E D ; Zhou, Junhua ; Maniero, Carmela ; Zhao, Wanfeng ; Kang, Soosung ; Silverman, Richard B. ; Elena Aisha, Azizan ; Brown, Morris J. / Regulation of aldosterone secretion by Ca v 1.3. In: Scientific Reports. 2016 ; Vol. 6.
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