title: Voltage-gated calcium channels in the human adrenal and primary aldosteronism.
abstract: Calcium channel blockers can efficiently be used in the treatment of primary aldosteronism (PA) related hypertension, but details on the localization of calcium channel (CC) in the human adrenal and its disorders, including PA, have remained unclear. Therefore, in this study we analyzed the known α subunits of L-, N- and T-type CCs in 74 adrenocortical aldosterone-producing adenomas (APA) and 16 cortisol-producing adenomas (CPA) using quantitative RT-PCR (qPCR). We also examined the status of L-(CaV1.2, CaV1.3), N-(CaV2.2) and T-(CaV3.2) CC subunits in five non-pathological adrenals (NA), five idiopathic hyperaldosteronism (IHA) cases, and 50 APA using immunohistochemistry. After qPCR evaluation, only CaV1.2, CaV1.3, CaV2.2, and CaV3.2 mRNA levels could be detected in APA and CPA. Among those, only CaV3.2 mRNA levels were significantly correlated with plasma aldosterone levels (P=0.0031), CYP11B2 expression levels (P<0.0001) and the presence of KCNJ5 mutations (P=0.0019) in APA. The immunolocalization of CCs in NA and IHA was detected in the zona glomerulosa (ZG), with a predominance of CaV3.2 in APA. These findings suggest that different types of CC can be involved in calcium-related aldosterone biosynthesis.
authors.affiliation: Department of Pathology, Tohoku University Graduate school of Medicine, Sendai, Japan.
authors.forename: Saulo J A
authors.initials: SJ
authors.lastname: Felizola
authors.affiliation: Department of Pathology, Tohoku University Graduate school of Medicine, Sendai, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Maekawa
authors.affiliation: Department of Pathology, Tohoku University Graduate school of Medicine, Sendai, Japan. Electronic address: yasu-naka@patholo2.med.tohoku.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Hospital, Sendai, Japan.
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Satoh
authors.affiliation: Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Hospital, Sendai, Japan.
authors.forename: Yoshikiyo
authors.initials: Y
authors.lastname: Ono
authors.affiliation: Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Hospital, Sendai, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Kikuchi
authors.affiliation: R&D Planning Department, Ajinomoto Co., Inc., Kawasaki, Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Aritomi
authors.affiliation: Division of Molecular Cell Biology, Core Research Facilities for Basic Sciences, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Yoshimura
authors.affiliation: Division of Diabetes and Endocrinology, Department of Internal Medicine, The Jikei University Kashiwa Hospital, Tokyo, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Tojo
authors.affiliation: Department of Pathology, Tohoku University Graduate school of Medicine, Sendai, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism*; D000302:Adrenal Cortex / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D006929:Hyperaldosteronism / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D021122:Protein Subunits; D012333:RNA, Messenger; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D006854:Hydrocortisone
keywords: Adrenal cortex; Aldosterone; Aldosterone producing adenoma; Calcium channel; Immunohistochemistry