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New paradigms in adenosine receptor pharmacology: allostery, oligomerization and biased agonism
Author(s) -
Vecchio Elizabeth A,
Baltos JoAnne,
Nguyen Anh T N,
Christopoulos Arthur,
White Paul J,
May Lauren T
Publication year - 2018
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.14337
Subject(s) - allosteric regulation , g protein coupled receptor , homomeric , adenosine receptor , agonism , functional selectivity , molecular pharmacology , receptor , drug discovery , drug action , adenosine , neuroscience , biology , pharmacology , agonist , biochemistry , drug , protein subunit , politics , political science , law , gene
Adenosine receptors are a family of GPCRs containing four subtypes (A 1 , A 2A , A 2B and A 3 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.