Multidrug Resistance Protein 1
| Multidrug Resistance Protein 1 | ||
|---|---|---|
|
||
| Properties of human protein | ||
| Mass / length primary structure | 1280 amino acids | |
| Secondary to quaternary structure | multipass membrane protein | |
| Identifier | ||
| Gene names | ABCB1 ; ABC20; CD243; CLCS; GP170; MDR1; MGC163296; P-gp; PGY1 | |
| External IDs | ||
| Transporter classification | ||
| TCDB | 3.A.1.201.1 | |
| designation | ABC transporter class B | |
| Enzyme classification | ||
| EC, category | 3.6.3.44 , hydrolase | |
| Substrate | ATP + H 2 O + xenobiotic (In) | |
| Products | ADP + phosphate + xenobiotic (Out) | |
| Occurrence | ||
| Parent taxon | Animals, fungi, bacteria | |
| Orthologue | ||
| human | House mouse | |
| Entrez | 5243 | 18671 |
| Ensemble | ENSG00000085563 | ENSMUSG00000040584 |
| UniProt | P08183 | P21447 |
| Refseq (mRNA) | NM_000927 | NM_011076 |
| Refseq (protein) | NP_000918 | NP_035206 |
| Gene locus | Chr 7: 87.5 - 87.71 Mb | Chr 5: 8.66 - 8.75 Mb |
| PubMed search | 5243 |
18671
|
The multidrug resistance protein 1 (MDR1) (also: PGP pump wherein PGP for p ermeability g Lyco p rotein is) is a protein in the cell membrane of the cells of animals , fungi and bacteria . It forms an active transporter that pumps cell-toxic substances out of the cell while consuming ATP . MDR1 belongs to the family of multidrug resistance-related proteins found in eukaryotes and bacteria , which in turn make up class B of the ABC transporters . In humans, the protein is expressed in the liver , kidneys , small intestine and brain . Mutations in the ABCB1 - gene may lead to increased susceptibility to type 13 of chronic inflammatory bowel disease lead (IBD13).
The PGP pump has the following effects:
- Cytostatic agents are represented by the PGP pump from the tumor cell is discharged
- Antibiotics are represented by the PGP pump from the bacterium discharged
- Neurotoxins are discharged from the brain cells via the blood-brain barrier into the bloodstream for metabolic disposal by the PGP pump (see loperamide ).
- When administered orally, medicinal products can have a reduced bioavailability due to their affinity for MDR1 .
In the first two cases, the PGP pump is extremely undesirable. Research has already been carried out to find a means to selectively deactivate the PGP pump. These include well-known drugs such as verapamil or new drugs such as elacridar . One tries z. B. to couple active ingredients to monoclonal antibodies (mAb) and thus direct them specifically to tumor cells. The antibody binds to surface receptors , which are then internalized (taken up) by the cell. In the cell, the active ingredient is split off from the antibody and unfolds its effect. In this case the PGP pump can be bypassed. Another approach is to stop the expression of the efflux pump .
The PGP pump is inhibited by the following drugs, among others:
- Amiodarone
- Azithromycin
- Captopril
- Clarithromycin
- Ciclosporin
- Piperine
- Quercetin
- Quinidine
- quinine
- Reserpine
- Ritonavir
- Tariquidar
- Verapamil
literature
- Stefan Oetzel: Drug pump outside . Pharmaceutical newspaper , 2012, issue 15.
- Christine Greiner: P-Glycoprotein - Importance for the drug metabolism NeuroTransmitter 2010, edition 9.
- Petra Zagermann-Muncke: When drugs influence transport proteins . Pharmaceutical newspaper, 2006, issue 50.
Individual evidence
- ↑ Entry at TCDB
- ↑ UniProt P08183
- ^ Pharmaceutical newspaper
- ^ Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers . Retrieved December 7, 2014.