Sensitivity of P-glycoprotein tryptophan residues to benzodiazepines and ATP interaction

• Type: Article in International Scientific Journal
• Date: 2007

Authors

Sofia A C Lima (Author) Other; Anabela Cordeiro da Silva (Author) FFUP; Baltazar de Castro (Author) FCUP; Paula Gameiro (Author) FCUP

Journal

Title: Biophysical Chemistry

Vol. 125 No. 1

Pages: 143-150

ISSN: 0301-4622

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 19 Citations

Scopus - 18 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-004-CMK

DOI: 10.1016/j.bpc.2006.07.006

Abstract (EN): Plasma membrane P-glycoprotein is a member of the ATP-binding cassette family of membrane transporters. In the present study tryptophan intrinsic fluorescence was used to understand the P-glycoprotein response to three benzodiazepines (bromazepam, chlordiazepoxide and flurazepam) in the presence and absence of ATP. Fluorescence emission spectra showed a red shift on the maximal emission wavelength upon interaction of P-glycoprotein with all benzodiazepines. Benzodiazepine association with nucleotide-bound P-glycoprotein also showed this trend and the quenching profile was attributed to a sphere-of-action model, for static fluorescence. Furthermore, quenching data of benzodiazepine-bound P-glycoprotein with ATP were concentration dependent and saturable, indicating that nucleotide binds to P-glycoprotein whether drug is present or not. These results seems in agreement with the proposal of the ATP-switch model by Higgins and Linton, where substrate binding to the transporters initiates the transport cycle by increasing the ATP binding affinity. (c) 2006 Elsevier B.V All tights reserved.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8