Mechanisms In Multi-Drug Resistance: ABC-transporters and detoxification enzymes I hepatocytes

The cellular components responsible for the phenomenon of multi-drug resistance (MDR) in the structural context of hepatocytes include intrinsic transmembrane proteins, generically called drug efflux pumps, and the enzymes responsible for detoxification and biotransformation of xenobiotics. The enzymes include the cytochrome P450s (CYPs) and the phase II conjugation enzymes such as glutathione-S-transferase (GST). The major drug efflux pumps are in the superfamily of ABC (ATP-binding-cassette)-transporters. Of these ABC-ATPases, the major subfamilies are the MDR/TAPs and MRPs (multi-drug resistance related proteins). The natural substrates are indicated for the drug efflux pumps.

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References:

Shabbits, J.A., et al., Molecular and pharmacological strategies to overcome Multidrug resistance. Expert Rev. Anticancer Ther., 1, 585-594 (2001).

Di, P.A., et al., Modulation by flavonoids of cell multidrug resistance mediated by P-glycoprotein and related ABC transporters. Cell. Mol. Life Sci., 59, 307-322 (2002).

Meier, P.J., and Stiger, B., Bile salt transporters. Annu. Rev. Physiol., 64, 635-661 (2002).