Hydrophobic vacuum cleaner

Two models have been developed to describe P-gp s unique transport activity. Higgins and Gottesman have postulated that P-gp acts as a hydrophobic vacuum cleaner, clearing the plasma membrane of substrates before they enter... 

Figure 9.35 Three proposed models of P-gp drug efflux, (a) The pore model, in which cytosolic drug is transported through a protein channel, (b) the flippase model, where drug associated with the inner leaflet of the membrane bilayer is flipped into the onter leaflet where it might passively diffuse out of the cell, and, (c) the hydrophobic vacuum cleaner model, where drug associated with the inner leaflet of the bilayer is exported out through the protein. (Reprinted with permission from Varma, M.V.S., et al. P-glycoprotein inhibitors and their screening A perspective from bioavailability enhancement. Pharmacol. Res. 2003, 48, 347-359, copyright 2003, Elsevier).

Fig. 9.15. Proposed mechanism by which P-glycoprotein (P-gp) secretes substrates. (1) Passive drug uptake across cell membrane. (2a) Formation of hydrophobic channel (pore) between the intracellular and extracellular space. (2b) Flippase activity, whereby the drug is flipped from the inner leaflet to the outer leaflet of the cell membrane. (2c) Vacuum cleaner model, in which drug interacts with P-gp in the lipid bilayer and is subsequently secreted back into the extracellular space. (From Matheney C, Lamb M, Brouwer K, et al. Pharmacokinetics and pharmacodynamic implications of P-glycoprotein modulation. Reviews of Therapeutics 2001 21 778-796 with permission.)...

---