دورية أكاديمية
Regulation of aldosterone secretion by Cav1.3.
العنوان: | Regulation of aldosterone secretion by Cav1.3. |
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المؤلفون: | Xie CB; Clinical Pharmacology Unit, University of Cambridge, Box 110, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK., Shaikh LH; Clinical Pharmacology Unit, University of Cambridge, Box 110, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK., Garg S; Clinical Pharmacology Unit, University of Cambridge, Box 110, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK., Tanriver G; Clinical Pharmacology Unit, University of Cambridge, Box 110, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK., Teo AE; Clinical Pharmacology Unit, University of Cambridge, Box 110, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK., Zhou J; Clinical Pharmacology Unit, University of Cambridge, Box 110, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK., Maniero C; Clinical Pharmacology Unit, University of Cambridge, Box 110, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK., Zhao W; Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK., Kang S; Department of Chemistry, Chemistry of Life Processes Institute, and Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, Illinois 60208-3113, USA., Silverman RB; Department of Chemistry, Chemistry of Life Processes Institute, and Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, Illinois 60208-3113, USA., Azizan EA; Clinical Pharmacology Unit, University of Cambridge, Box 110, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK.; Department of Medicine, Faculty of Medicine, The National University of Malaysia (UKM) Medical Centre, Kuala Lumpur 56000, Malaysia., Brown MJ; Clinical Pharmacology Unit, University of Cambridge, Box 110, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK.; Barts Heart Centre, William Harvey Research Institute, Queen Mary University London, London EC1M 6BQ, UK. |
المصدر: | Scientific reports [Sci Rep] 2016 Apr 21; Vol. 6, pp. 24697. Date of Electronic Publication: 2016 Apr 21. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : Nature Publishing Group, copyright 2011- |
مواضيع طبية MeSH: | Aldosterone/*metabolism , Calcium Channels, L-Type/*metabolism, Calcium Channel Blockers/pharmacology ; Calcium Channels, L-Type/genetics ; Cell Line ; Cells, Cultured ; Genotype ; Humans ; Mutation ; Nifedipine/pharmacology ; Protein Transport |
مستخلص: | Aldosterone-producing adenomas (APAs) vary in phenotype and genotype. Zona glomerulosa (ZG)-like APAs frequently have mutations of an L-type calcium channel (LTCC) CaV1.3. Using a novel antagonist of CaV1.3, compound 8, we investigated the role of CaV1.3 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, CaV1.2, over CaV1.3. In H295R cells transfected with wild-type or mutant CaV1.3 channels, the latter produced more aldosterone than wild-type, which was ameliorated by 100 μM of compound 8. In primary adrenal and non-transfected H295R cells, compound 8 decreased aldosterone production similar to high concentration of nifedipine (100 μM). Selective CaV1.3 blockade may offer a novel way of treating primary hyperaldosteronism, which avoids the vascular side effects of CaV1.2-blockade, and provides targeted treatment for ZG-like APAs with mutations of CaV1.3. |
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معلومات مُعتمدة: | FS/11/35/28871 United Kingdom BHF_ British Heart Foundation; FS/14/12/30540 United Kingdom BHF_ British Heart Foundation; 085686/Z/08/A United Kingdom WT_ Wellcome Trust; United Kingdom WT_ Wellcome Trust; FS/14/75/31134 United Kingdom BHF_ British Heart Foundation |
المشرفين على المادة: | 0 (CACNA1D protein, human) 0 (Calcium Channel Blockers) 0 (Calcium Channels, L-Type) 4964P6T9RB (Aldosterone) I9ZF7L6G2L (Nifedipine) |
تواريخ الأحداث: | Date Created: 20160422 Date Completed: 20170309 Latest Revision: 20230722 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC4876952 |
DOI: | 10.1038/srep24697 |
PMID: | 27098837 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2045-2322 |
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DOI: | 10.1038/srep24697 |