Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Click here for more information

Sign In to gain access to subscriptions and/or personal tools.
Journal of Biomolecular Screening
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
1087057109337937v1
1087057109337937v2
14/7/811    most recent
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (1)
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by van der Lee, M. M.C.
Right arrow Articles by Zaman, G. J.R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by van der Lee, M. M.C.
Right arrow Articles by Zaman, G. J.R.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Pharmacological Characterization of Receptor Redistribution and β-Arrestin Recruitment Assays for the Cannabinoid Receptor 1

Miranda M.C. van der Lee

Schering-Plough Research Institute, Molecular Pharmacology Unit, Oss, The Netherlands

Marion Blomenröhr

Schering-Plough Research Institute, Molecular Pharmacology Unit, Oss, The Netherlands

Antoon A. van der Doelen

Schering-Plough Research Institute, Molecular Pharmacology Unit, Oss, The Netherlands

Jesse W.Y. Wat

Schering-Plough Research Institute, Molecular Pharmacology Unit, Oss, The Netherlands

Niels Smits

Schering-Plough Research Institute, Molecular Pharmacology Unit, Oss, The Netherlands

Bonnie J. Hanson

Invitrogen Discovery Sciences, Madison, Wisconsin

Chris J. van Koppen

Schering-Plough Research Institute, Molecular Pharmacology Unit, Oss, The Netherlands

Guido J.R. Zaman

Schering-Plough Research Institute, Molecular Pharmacology Unit, Oss, The Netherlands, guido.zaman{at}spcorp.com

Receptor redistribution and β-arrestin recruitment assays provide a G-protein-subtype-independent method to measure ligand-stimulated activation of G-protein-coupled receptors. In particular β-arrestin assays are becoming an increasingly popular tool for drug discovery. The authors have compared a high-content-imaging-based Redistribution® assay and 2 nonimaging-based β-arrestin recruitment assays, TangoTM and PathHunter TM, for the cannabinoid receptor 1. Inasmuch as all 3 assays use receptors that are modified at the C-terminus, the authors verified their pharmacology via detection of G{alpha}i coupling of the receptor in cAMP assays using reference ligands. The potencies and efficacies of the cannabinoid receptor agonists CP55,940 and WIN55,212-2 correlated well between the 3 assays, and are comparable with the measured ligand binding affinities. The inverse agonist SR141716 decreased basal signal in all 3 assays, but only in the Tango bla assay a reliable EC50 could be determined for this compound, suggesting that Tango is the most suitable assay for the identification of new inverse agonists. Both the Redistribution and the PathHunter assay could discriminate partial agonists from full agonists, whereas in the Tango assay partial agonists behaved as full agonists. Only the PathHunter cells allowed detection of cannabinoid receptor activation via β-arrestin recruitment and G{alpha}i-protein-mediated inhibition of cAMP, thus enabling the identification of biased ligands that differ in these cellular effects. The characteristics and limitations of the different assays are discussed. (Journal of Biomolecular Screening 2009:811-823)

Key Words: cannabinoid receptor 1 • redistribution • β-arrestin recruitment

This version was published on August 1, 2009

Journal of Biomolecular Screening, Vol. 14, No. 7, 811-823 (2009)
DOI: 10.1177/1087057109337937
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
A. Kapur, P. Zhao, H. Sharir, Y. Bai, M. G. Caron, L. S. Barak, and M. E. Abood
Atypical Responsiveness of the Orphan Receptor GPR55 to Cannabinoid Ligands
J. Biol. Chem., October 23, 2009; 284(43): 29817 - 29827.
[Abstract] [Full Text] [PDF]