Membrane Transporters & Drug Response
ABC & SLC transporters in pharmacokinetics, drug targeting, resistance and adverse drug responses
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Introduction & pharmacological importance
- Membrane transporters — integral membrane proteins that control influx of nutrients/ions and efflux of waste, toxins, drugs and other xenobiotics; ~2000 genes (~7% of the human genome) encode transporters or transporter-related proteins.
- Two superfamilies — pharmacologically the field centres on ABC (ATP-binding cassette) primary-active efflux pumps and SLC (solute carrier) facilitative / secondary-active carriers.
- Four pharmacological dimensions — (1) Pharmacokinetics — selective absorption/elimination in gut, liver and kidney + protective barriers; (2) Pharmacodynamics — transporters as drug targets (SERT, SGLT2); (3) Drug resistance — efflux/influx changes in cancer, HIV, epilepsy; (4) Adverse responses — control cellular drug exposure → toxicity and drug–drug interactions (DDIs).
- Membrane basis — a ~100 Å phospholipid + cholesterol bilayer (fluid-mosaic) of high electrical resistance and relative impermeability; aqueous pores and paracellular spaces allow some small-molecule passage.
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Membrane Transporters
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