P-glycoprotein efflux transporter activity often displays biphasic dose-response relationships.
The occurrence of P-glycoprotein efflux transporter systems is recognized as playing critical roles in chemotherapy, drug pharmacokinetics, and the bioavailability of environmental toxins. This article reveals that P-glycoprotein efflux transporter activity commonly displays a biphasic dose response, with low doses being stimulatory and high doses inhibiting. The quantitative features of these biphasic dose responses are consistent with the hormetic dose-response model and are independent of biological model and chemical class. These findings provide further support for the generalizability of the hormetic dose-response model while having important biological and clinical implications, including transport through the blood-brain barrier.
Environmental Health Sciences Division, School of Public Health, University of Massachusetts, Amherst, Massachusetts 01003, USA. edwardc@schoolph.umass.edu
Edward J
EJ
Calabrese
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D001682:Biological Availability; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004364:Pharmaceutical Preparations