Journal
ACS CHEMICAL NEUROSCIENCE
Volume 2, Issue 2, Pages 82-89Publisher
AMER CHEMICAL SOC
DOI: 10.1021/cn100078a
Keywords
Positron emission tomography; drug transporters; P-glycoprotein; breast cancer resistance protein; blood-brain barrier; transport inhibitors; tariquidar
Funding
- National Institutes of Mental Health [Z01-MH-002852-04, MH002793-09]
- National Cancer Institute at the National Institutes of Health [Z01-BC-005598, Z01-BC-010030-12]
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Tariquidar was developed as a specific inhibitor of the efflux transporter ABCB1. Recent positron emission tomographic brain imaging studies using [C-11]-tariquidar to measure ABCB1 (P-gp, P-glycoprotein) density in mice indicate that the inhibitor may not be as specific as previously thought. We examined its selectivity as an inhibitor and a substrate for the human transporters P-gp, breast cancer resistance protein (BCRP, ABCG2), and multidrug resistance protein 1 (MRP1, ABCC1). Our results show that at low concentrations, tariquidar acts selectively as an inhibitor of P-gp and also as a substrate of BCRP. At much higher concentrations (>= 100 nM), tariquidar acts as an inhibitor of both P-gp and BCRP. Thus, the in vivo specificity of tariquidar depends on concentration and the relative density and capacity of P-gp vs BCRP.
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