ArticleMolecular endocrinology (Baltimore, Md.)2011
Vitamin D receptor (VDR) regulation of voltage-gated chloride channels by ligands preferring a VDR-alternative pocket (VDR-AP).
Article in Molecular endocrinology (Baltimore, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 67 citations in OpenAlex.
- Combination therapy with nutritional vitamin D and calcimimetics in secondary hyperparathyroidism: a mechanism-based approach to restoring PTH regulation.Frontiers in nutrition · 2026Review
- Importance of vitamin D in gastrointestinal health and disease.Frontiers in nutrition · 2026Review
- Review
- A novel chemo-phenotypic method identifies mixtures of salpn, vitamin D3, and pesticides involved in the development of colorectal and pancreatic cancer.Ecotoxicology and environmental safety · 2022Article
- Role of Specialized Pro-resolving Mediators in Reducing Neuroinflammation in Neurodegenerative Disorders.Frontiers in aging neuroscience · 2022Review
- The Relationship Between Vitamin D and Postoperative Atrial Fibrillation: A Prospective Cohort Study.Frontiers in nutrition · 2022Article
- A Novel Method for the Determination of Vitamin D Metabolites Assessed at the Blood-Cerebrospinal Fluid Barrier.Biomolecules · 2021Article
- Cytotoxicity of glucoevatromonoside alone and in combination with chemotherapy drugs and their effects on NaMolecular and cellular biochemistry · 2021Article
- Resolution of Inflammation in Neurodegenerative Diseases: The Role of Resolvins.Mediators of inflammation · 2020Review
- A Narrative Role of Vitamin D and Its Receptor: With Current Evidence on the Gastric Tissues.International journal of molecular sciences · 2019Review
- Vitamin D Deficiency During Pregnancy and Autism Spectrum Disorders Development.Frontiers in psychiatry · 2019Review
- Vitamin D Receptor Is Necessary for Mitochondrial Function and Cell Health.International journal of molecular sciences · 2018Article
- 27-Hydroxycholesterol Is an Estrogen Receptor β-Selective Negative Allosteric Modifier of 17β-Estradiol Binding.Endocrinology · 2018Article
- Calcitriol, the Bioactive Metabolite of Vitamin D, Increases Ventricular KFrontiers in physiology · 2018Article
- Role of Placental VDR Expression and Function in Common Late Pregnancy Disorders.International journal of molecular sciences · 2017Review
- 1,25(OH)2 vitamin D3 signalling on immature rat Sertoli cells: gamma-glutamyl transpeptidase and glucose metabolism.Journal of cell communication and signaling · 2017Article
- Effect ofInternational journal of rheumatology · 2017Article
- Interactions between oestrogen and 1α,25(OH)Basic and clinical andrology · 2017Article
- The conformational dynamics of H2-H3n and S2-H6 in gating ligand entry into the buried binding cavity of vitamin D receptor.Scientific reports · 2016Article
- Mechanisms of vitamin D₃ metabolite repression of IgE-dependent mast cell activation.The Journal of allergy and clinical immunology · 2014Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
We have postulated that the vitamin D receptor (VDR) contains two overlapping ligand binding sites, a genomic pocket and an alternative pocket (AP), that mediate regulation of gene transcription and rapid responses, respectively. Flexible VDR + ligand docking calculations predict that the major blood metabolite, 25(OH)-vitamin D(3) (25D3), and curcumin (CM) bind more selectively to the VDR-AP when compared with the seco-steroid hormone 1α,25(OH)(2)-vitamin D(3) (1,25D3). In VDR wild-type-transfected COS-1 cells and TM4 Sertoli cells, 1,25D3, 25D3, and CM each trigger voltage-gated, outwardly rectifying chloride channel (ORCC) currents that can be blocked by the VDR antagonist 1β,25(OH)(2)-vitamin D(3) and the chloride channel antagonist (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid). VDR mutational analysis in transfected COS-1 cells demonstrate the DNA-binding domain is not, but the ligand binding and hinge domains of the VDR are, required for 1,25D3 and 25D3 to activate the ORCC. Dose-response studies demonstrate that 25D3 and 1,25D3 are approximately equipotent in stimulating ORCC rapid responses, whereas 1 nm 1,25D3 was 1000-fold more potent than 25D3 and CM in stimulating gene expression. The VDR-AP agonist effects of 1,25D3, 25D3, and low-dose CM are lost after pretreatment of TM4 cells with VDR small interfering RNA. Collectively, these results are consistent with an essential role for the VDR-AP in initiating the signaling required for rapid opening of ORCC. The fact that 25D3 is equipotent to 1,25D3 in opening ORCC suggests that reconsideration of the ability of 25D3 to generate biological responses in vivo may be in order.
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