The role of multi-drug resistance p-glycoprotein in glucocorticoid function: Studies in animals and relevance in humans
Abstract
Entry of glucocorticoid hormones into cells is tightly regulated by membrane transporters. One of these transporters, the multi-drug resistance p-glycoprotein, has been extensively described to confer treatment resistance to tumour cells as well as to regulate the intracellular levels of glucocorticoid hormones. Moreover, multi-drug resistance p-glycoprotein is also present on the endothelial cells of the blood-brain-barrier, and in neurones, where it limits the access of glucocorticoids to the brain. Finally, this transporter also has the ability to limit the entry of some antidepressants to the brain, with potential consequences for the clinical therapeutic effects of these drugs. This review will focus on the studies that have used multi-drug resistance p-glycoprotein knockout animals in such context, and will discuss the potential clinical relevance of these transporters for psychiatric disorders. In particular, we will discuss the reciprocal interactions between this transporter and antidepressants, both as its inhibitors and as its substrates. We believe that the interaction between antidepressants and multi-drug resistance p-glycoprotein is one of the most potentially exciting developments in psychopharmacological research.
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Innate immune cytokines, including TNF-α, are capable of influencing activity of the p-glycoprotein (multidrug resistance) pump, which pumps the glucocorticoids, cortisol and DEX, out of the cell, while having no effect on corticosterone or RU38486.
“innate immune cytokines, including TNF-α, are capable of influencing activity of the p-glycoprotein (multidrug resistance) pump, which pumps the glucocorticoids, cortisol and DEX, out of the cell, while having no effect on corticosterone or RU38486.83”
From Cytokines and Glucocorticoid Receptor Signaling (2009) · cites this paper as [83]
Cites
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Self-citationGlucocorticoid Receptor Function<i>In Vitro</i>in Patients with Major Depression
Pariante, C. M. (2004) · Stress · doi:10.1080/10253890500069650 · Cited by 147 · see citing works
Self-citationPariante, C. M., Hye, A., Williamson, R., Makoff, A., Lovestone, S., & Kerwin, R. W. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300195 · Cited by 70 · see citing works
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Cytokines and Glucocorticoid Receptor Signaling
Pace, T. W. W., & Miller, A. H. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04984.x · Cited by 339 · see citing works
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- Authors
- Pariante, C. M.
- Affiliations
- King's College London (GB)
- Corresponding author
- Pariante, Carmine M.
- ORCID
- Pariante, Carmine M.
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 583
- Issue
- 2-3
- Pages
- 263-271
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W2094716450
- Cited by
- 58
- References
- 3
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 3 · 2015: 4 · 2013: 2 · 2012: 6
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- multidrug resistance protein 1, P-glycoprotein, membrane transporters, blood-brain barrier, antidepressant resistance, mental illness
- MeSH terms
- Animals, Antidepressive Agents, Mental Disorders, Glucocorticoids, Humans, Species Specificity, Mice, Knockout, Drug Resistance, Multiple, ATP Binding Cassette Transporter, Subfamily B, Mice
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