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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2007

Autores

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

Revista

Título: Biophysical Chemistry

Vol. 125 Nº 1

Páginas: 143-150

ISSN: 0301-4622

Editora: Elsevier

Indexação

ISI Web of Knowledge - 19 Citações

Scopus - 18 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 8