Fluorescence correlation spectroscopy in drug discovery: study of Alexa532-endothelin 1 binding to the endothelin ETA receptor to describe the pharmacological profile of natural products.

ABSTRACT: Fluorescence correlation spectroscopy and the newly synthesized Alexa532-ET1 were used to study the dynamics of the endothelin ET(A) receptor-ligand complex alone and under the influence of a semisynthetic selective antagonist and a fungal extract on living A10 cells. Dose-dependent increase of inositol phosphate production was seen for Alexa532-ET1, and its binding was reduced to 8% by the selective endothelin ET(A) antagonist BQ-123, confirming the specific binding of Alexa532-ET1 to the endothelin ET(A) receptor. Two different lateral mobilities of the receptor-ligand complexes within the cell membrane were found allowing the discrimination of different states for this complex. BQ-123 showed a strong binding affinity to the "inactive" receptor state characterized by the slow diffusion t

SUBMITTER: Caballero-George C 

PROVIDER: S-EPMC3353486 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature