Multidrug Resistance-Related Proteins
| Multidrug Resistance-Related Proteins | ||
|---|---|---|
| Identifier | ||
| Gene name (s) | ABCC ; MDR | |
| Transporter classification | ||
| TCDB | 3.A.1.208 | |
| designation | ABC transporter type C | |
| Occurrence | ||
| Parent taxon | Eukaryotes | |
The group of Multidrug Resistance-Related Proteins (MRP) consists of several genetically related transmembrane proteins that pump substances out of cells while consuming energy. They occur in all eukaryotes and form class C of the large family of so-called ABC transporters .
Today nineteen individual proteins are known, nine of which occur in humans (MRP1 to MRP9). The corresponding gene names begin with ABCC . The common features of the proteins lie in their function: As part of the cell membrane , they are able to transport various endogenous and toxic substances out of the cell while consuming energy (hydrolysis of ATP ) . Individual drugs are another substrate for MRP. This means that the cell can naturally protect itself from harmful substances by simply transporting them back out of the cell interior.
MRPs therefore also play a decisive role in pharmacokinetic issues. MRPs (also called efflux pumps) are found at many physiological barriers, such as: B. blood-brain barrier , intestine , kidney and liver . For example, MRP-2 is responsible for bilirubin excretion in the bile . In combination drug therapy (here in the example with two drugs), interactions between the drugs often occur. A possible mechanism for this can be the inhibition of individual efflux pumps by an active substance. This can lead to less excretion of the other active ingredient and thus to an increase in concentration.
Story of discovery
The phenomenon that ultimately led to the discovery of MRP is called multidrug resistance (MDR) and was first observed in malignant tumor cells . When treating a tumor with a single chemotherapeutic agent , the therapy was initially successful and the tumor shrank. However, as treatment progressed, the tumor cells became resistant to the chemotherapy drug and began to grow again.
With the help of cell cultures from tumors it could be shown that the onset of resistance was not limited to the individual chemotherapeutic agent. Despite treatment with only one chemotherapy agent, the tumor became resistant to several classes of chemotherapy agents in a short period of time. The amazing thing about this discovery, however, was that the tumor had never come into contact with any of the other chemotherapy drugs before. Furthermore, the preparations differed extremely from each other, especially in the mechanism of action. So how could a tumor develop such widespread resistance in a short period of time?
After intensive research, the MRP were discovered and clarified. According to the model described above, the proteins were initially successfully detected on tumor cell lines. The theory that MRPs are involved in the development of an MDR has been supported by further research in this area. A massively increased expression of MRP was found in cell lines in whose culture medium chemotherapeutic agents were added.
pharmacology
The role of MRP in clinical medicine is still unclear. For example, the individual dosage of a drug would be of future significance . If a drug is to work inside the cell, it must also be dosed accordingly. In this context, it is conceivable that individuals have different levels of MRP activity and are therefore more or less sensitive to individual drugs. In the therapy of cancer , too , the discovery and research of MRP has so far not brought much progress.
Individual evidence
Web links
- Review article on MDR (Engl.)
- Cancer Index