P-gp (P-glycoprotein), also known as ACBB1 - ATP Bindig Cassette Subfamily B Member 1 -, is an important transport protein in the cell membrane. It belongs to the family of ABC transporters, ATP-dependent efflux transporters (ABC transporters/external transporters - see transporters below) and plays a central role in drug transport and metabolism.
P-glycoprotein
DefinitionThis section has been translated automatically.
General informationThis section has been translated automatically.
ABC transporters always transport endogenous substances such as testosterone, progesterone or pharmaceuticals from the cell into the extracellular space.
Many pharmacologically active substances are substrates of P-gp, for example:
- Doxorubicin
- digoxin
- Cyclosporin A
- loperamide
- HIV protease inhibitors
OccurrenceThis section has been translated automatically.
Occurrence in the body: P-gp is widely distributed, e.g. in: intestinal epithelium (limits oral bioavailability), liver (promotes biliary excretion), kidney (promotes renal elimination), blood-brain barrier (prevents penetration into the brain), placenta (protects the fetus from xenobiotics)
PathophysiologyThis section has been translated automatically.
As the substrates of ABC transporters are transported against a concentration gradient, energy must be expended for the transport process. All ABC transporters (49 are known to date) obtain this energy by binding an ATPase. This means that they hydrolyze ATP themselves. ABC transporters can therefore be regarded as membrane-bound ATPases.
ABC transporters play a major role in the development of resistance of bacteria to antibiotics (Theodoulou FL et al. 2015). In plants in the development of resistance to herbicides. Mutations in a coding transporter gene lead to various metabolic diseases. Overexpression of ABC transporters in tumor tissues can lead to a non-response to chemotherapeutics.
CFTR is an exception. In CFTR = Cystic Fibrosis Transmembrane Conductance Regulator, the ABC cassette only controls the opening and closing of a chloride ion channel. Mutations in the CFTR gene lead to the clinical picture of cystic fibrosis.
ClinicThis section has been translated automatically.
Multidrug resistance (MDR): Many tumor cells overexpress P-gp, leading to resistance to chemotherapeutic agents.
Interactions: Drugs that inhibit or induce P-gp can strongly influence the plasma concentration of other drugs.
LiteratureThis section has been translated automatically.
- Kim RB (2002) Drugs as P-glycoprotein substrates, inhibitors, and inducers. Drug Metab Rev 34(1-2):47-54.
- Lin JH (2003). Drug-drug interaction mediated by inhibition and induction of P-glycoprotein. Adv Drug Deliv Rev 55:53-81.
- Lin JH et al. (2003) Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin Pharmacokinet 42:59-98.