P-glycoprotein
From Wikipedia, the free encyclopedia
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ATP-binding cassette, sub-family B (MDR/TAP), member 1
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| Identifiers | |
| Symbol | ABCB1 PGY1, MDR1, CLCS |
| HUGO | 40 |
| Entrez | 5243 |
| OMIM | 171050 |
| RefSeq | NM_000927 |
| UniProt | P08183 |
| Other data | |
| Locus | Chr. 7 q21.12 |
P-glycoprotein (abbreviated as P-gp or Pgp, also called ABCB1, ATP-binding cassette sub-family B member 1, MDR1, P-glycoprotein, and PGY1) is a well characterized human ABC-transporter of the MDR/TAP subfamily. It is extensively distributed and expressed in normal cells such as those lining the intestine, liver cells, renal proximal tubular cells, and capillary endothelial cells comprising the blood brain barrier.
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[edit] Function
ABCB1 is an ATP-dependent efflux pump with broad substrate specificity. It likely evolved as a defence mechanism against harmful substances.
ABCB1 transports various substrates across the cell membrane including:
- Drugs such as colchicine and tacrolimus
- Chemotherapeutic agents such as etoposide, adriamycin, and vinblastine;
- Lipids
- Steroids
- Xenobiotics
- Peptides
- Bilirubin
- Cardiac glycosides like digoxin
- Immunosuppressive agents
- Glucocorticoids like dexamethasone
- HIV-type 1 antiretroviral therapy agents like protease inhibitors and nonnucleoside reverse transcriptase inhibitors.
Its ability to transport the above substrates accounts for the many roles of ABCB1 including:
- Regulating the distribution and bioavailability of drugs
- Increased intestinal expression of P-glycoprotein can reduce the absorption of drugs that are substrates for P-glycoprotein. Thus, there is a reduced bioavailability, therapeutic plasma concentrations are not attained. On the other hand, supratherapeutic plasma concentrations and drug toxicity may result because of decreased P-glycoprotein expression
- Active cellular transport of antineoplastics resulting in multidrug resistance to these drugs
- The removal of toxic metabolites and xenobiotics from cells into urine, bile and the intestinal lumen
- The transport of compounds out of the brain across the blood-brain barrier
- Digoxin uptake
- Prevention of ivermectin entry into the central nervous system
- The migration of dendritic cells
- Protection of hematopoietic stem cells from toxins.
[edit] Structure
Pgp is a 170 kDa transmembrane glycoprotein which includes 10-15 kDa of N-terminal glycosylation. The N-term half of the molecule contains 6 transmembrane domains, followed by a large cytoplasmic domain with an ATP binding site, and then a second section with 6 transmembrane domains and an ATP binding site which shows over 65% of amino acid similarity with the first half of the polypeptide.
[edit] History
ABCB1 was first cloned and characterized using its ability to confer a multidrug resistance phenotype to cancer cells that had developed resistance to chemotherapy drugs.
[edit] References
- ↑ NCBI
- ↑ Dean, Michael. The Human ATP-Binding Cassette (ABC) Transporter Superfamily. Bethesda (MD):National Library of Medicine (US), NCBI; 2002 November.
- ↑ Juliano R.L., Ling V.A. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim. Biophys. Acta. 455:152-162; 1976 Entrez PubMed 990323
- ↑ Viguié F . ABCB1. Atlas Genet Cytogenet Oncol Haematol. March 1998 [5]
