ArticlePharmaceutical research2015
Vitamin D receptor activation induces P-glycoprotein and increases brain efflux of quinidine: an intracerebral microdialysis study in conscious rats.
Article in Pharmaceutical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 23 citations in OpenAlex.
- Pharmacokinetic Drug Interaction Between Raloxifene and Cholecalciferol in Healthy Volunteers.Clinical pharmacology in drug development · 2022Trial
- Significance of the Vitamin D Receptor on Crosstalk with Nuclear Receptors and Regulation of Enzymes and Transporters.The AAPS journal · 2022Review
- Full spectrum of vitamin D immunomodulation in multiple sclerosis: mechanisms and therapeutic implications.Brain communications · 2022Review
- A new approach to produce [EJNMMI radiopharmacy and chemistry · 2021Article
- Brain Endothelial P-Glycoprotein Level Is Reduced in Parkinson's Disease via a Vitamin D Receptor-Dependent Pathway.International journal of molecular sciences · 2020Article
- Vitamin D3 Is Transformed into 1,25(OH)2D3 by Triggering CYP3A11(CYP3A4) Activity and Hydrolyzing Midazolam.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Role of vitamin D receptor in the regulation ofActa pharmaceutica Sinica. B · 2019Review
- Calcitriol and Calcipotriol Modulate Transport Activity of ABC Transporters and Exhibit Selective Cytotoxicity in MRP1-overexpressing Cells.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Intranasal administration of vitamin D attenuates blood-brain barrier disruption through endogenous upregulation of osteopontin and activation of CD44/P-gp glycosylation signaling after subarachnoid hemorrhage in rats.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- [Research advances in association between vitamin D and Kawasaki disease and related mechanisms of action].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2016Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
purposeSince the vitamin D receptor (VDR) was found to up-regulate cerebral P-glycoprotein expression in vitro and in mice, we extend our findings to rats by assessing the effect of rat Vdr activation on brain efflux of quinidine, a P-gp substrate that is eliminated primarily by cytochrome P450 3a.
methodsWe treated rats with vehicle or the active VDR ligand, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] (4.8 or 6.4 nmol/kg i.p. every 2nd day × 4) and examined P-gp expression and cerebral quinidine disposition via microdialysis in control and treatment studies conducted longitudinally in the same rat.
resultsThe 6.4 nmol/kg 1,25(OH)2D3 dose increased cerebral P-gp expression 1.75-fold whereas hepatic Cyp3a remained unchanged. Although there was no change in systemic clearance elicited by 1,25(OH)2D3, brain extracellular fluid quinidine concentrations were lower in treated rats. We noted that insertion of indwelling catheters increased plasma protein binding of quinidine and serial sampling decreased the blood:plasma concentration ratio, factors that alter distribution ratios in microdialysis studies. After appropriate correction, KECF/P,uu and KECF/B,uu, or ratios of quinidine unbound concentrations in brain extracellular fluid to plasma or blood at steady-state, were more than halved.
conclusionWe demonstrate that VDR activation increases cerebral P-gp expression and delimits brain penetration of P-gp substrates.
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