J Clin Pharmacol
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First published on December 21, 2007, doi:10.1177/0091270007311568

The Journal of Clinical Pharmacology 2008;48:365.

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©© 2007 American College of Clinical Pharmacology, Inc.
The Journal of Clinical Pharmacology , 10.1177/0091270007311568

Article

P-glycoprotein: So Many Ways to Turn It On

Richard Callaghan 1*, Emily Crowley 1, Simon Potter 2, and Ian D. Kerr 2

1 University of Oxford
2 University of Nottingham

* To whom correspondence should be addressed. E-mail: richard.callaghan{at}ndcls.ox.ac.uk.


  Abstract
Expression of the ABC transporter P-glycoprotein (P-gp or ABCB1) is associated with resistance to chemotherapy in cancer. However, early investigations into the regulation of ABCB1 expression revealed that the process is not a classical induction as observed for certain metabolizing enzymes. The process involves the cellular stress response pathway initiated by either inflicted (eg, chemotherapy damage) or endogenous (eg, hypoxia) factors. However, ABCB1 is also expressed in a number of noncancerous tissues. In particular, the protein is found at tissues providing a barrier or secretory function. The localization of ABCB1 in normal tissues will impact significantly on drug pharmacokinetics, in particular the absorption and elimination processes. This review also describes the mechanism underlying ABCB1 expression in noncancerous tissue, a process that does not involve the stress response.
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