Hetero-oligomerization between adenosine A 1 and thromboxane A 2 receptors and cellular signal transduction on stimulation with high and low concentrations of agonists for both receptors

Natsumi Mizuno, Tokiko Suzuki, Noriyasu Hirasawa, Norimichi Nakahata

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Growing evidence indicates that G protein-coupled receptors can form homo- and hetero-oligomers to diversify signal transduction. However, the molecular mechanisms and physiological significance of G protein-coupled receptor-oligomers are not fully understood. Both ADOR1 (adenosine A 1 receptor) and TBXA2R (thromboxane A 2 receptor α; TPα receptor), members of the G protein-coupled receptor family, act on astrocytes and renal mesangial cells, suggesting certain functional correlations. In this study, we explored the possibility that adenosine A 1 and TPα receptors form hetero-oligomers with novel pharmacological profiles. We showed that these receptors hetero-oligomerize by conducting coimmunoprecipitation and bioluminescence resonance energy transfer (BRET 2) assays in adenosine A 1 receptor and TPα receptor-cotransfected HEK293T cells. Furthermore, coexpression of the receptors affected signal transduction including the accumulation of cyclic AMP and phosphorylation of extracellular signal-regulated kinase-1 and -2 was significantly increased by high and low concentrations of adenosine A 1 receptor agonist and TPα agonists, respectively. Our study provides evidence of hetero-oligomerization between adenosine A 1 and TPα receptors for the first time, and suggests that this oligomerization affects signal transduction responding to different concentrations of receptor agonists.

Original languageEnglish
Pages (from-to)5-14
Number of pages10
JournalEuropean Journal of Pharmacology
Volume677
Issue number1-3
DOIs
Publication statusPublished - 2012 Feb 29

Keywords

  • Adenosine A receptor
  • Cyclic AMP
  • Extracellular signal-regulated kinase
  • G protein-coupled receptor
  • Hetero-oligomer
  • Thromboxane A receptor

ASJC Scopus subject areas

  • Pharmacology

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