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ScientificWorldJournal. 2012;2012:524169. doi: 10.1100/2012/524169. Epub 2012 May 1.

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.

Author information

  • 1Department of Molecular Pharmacology and Pharmacognosy, Drug Discovery Center, Institute for Scientific Research and High Technology Services, Panama City, Panama. ccaballero@indicasat.org.pa

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 time constant. A similar effect was observed for the fungal extract, which completely displaced Alexa532-ET1 from its binding to the "inactive" receptor state. These findings suggest that both BQ-123 and the fungal extract act as inverse agonists.

PMID:
22623909
[PubMed - indexed for MEDLINE]
PMCID:
PMC3353486
Free PMC Article

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