Format

Send to

Choose Destination
Br J Pharmacol. 2018 Nov;175(21):4036-4046. doi: 10.1111/bph.14337. Epub 2018 Jun 21.

New paradigms in adenosine receptor pharmacology: allostery, oligomerization and biased agonism.

Author information

1
Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia.
2
Department of Pharmacology, Monash University, Melbourne, VIC, Australia.

Abstract

Adenosine receptors are a family of GPCRs containing four subtypes (A1 , A2A , A2B and A3 receptors), all of which bind the ubiquitous nucleoside adenosine. These receptors play an important role in physiology and pathophysiology and therefore represent attractive drug targets for a range of conditions. The theoretical framework surrounding drug action at adenosine receptors now extends beyond the notion of prototypical agonism and antagonism to encompass more complex pharmacological concepts. New paradigms include allostery, in which ligands bind a topographically distinct receptor site from that of the endogenous agonist, homomeric or heteromeric interactions across receptor oligomers and biased agonism, that is, ligand-dependent differential intracellular signalling. This review provides a concise overview of allostery, oligomerization and biased agonism at adenosine receptors and outlines how these paradigms may enhance future drug discovery endeavours focussed on the development of novel therapeutic agents acting at adenosine receptors.

LINKED ARTICLES:

This article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.21/issuetoc.

PMID:
29679502
PMCID:
PMC6177620
[Available on 2019-11-01]
DOI:
10.1111/bph.14337

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center