New paradigms in adenosine receptor pharmacology

allostery, oligomerization and biased agonism

Research output: Contribution to journalReview ArticleResearchpeer-review

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. 

Original languageEnglish
Pages (from-to)4036-4046
Number of pages11
JournalBritish Journal of Pharmacology
Volume175
Issue number21
DOIs
Publication statusPublished - 1 Nov 2018

Cite this

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title = "New paradigms in adenosine receptor pharmacology: allostery, oligomerization and biased agonism",
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. ",
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New paradigms in adenosine receptor pharmacology : allostery, oligomerization and biased agonism. / Vecchio, Elizabeth A.; Baltos, Jo Anne; Nguyen, Anh T.N.; Christopoulos, Arthur; White, Paul J.; May, Lauren T.

In: British Journal of Pharmacology, Vol. 175, No. 21, 01.11.2018, p. 4036-4046.

Research output: Contribution to journalReview ArticleResearchpeer-review

TY - JOUR

T1 - New paradigms in adenosine receptor pharmacology

T2 - allostery, oligomerization and biased agonism

AU - Vecchio, Elizabeth A.

AU - Baltos, Jo Anne

AU - Nguyen, Anh T.N.

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AU - White, Paul J.

AU - May, Lauren T.

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