Purinergic Signalling

, Volume 5, Issue 3, pp 289–298

Differential role of the carboxy-terminus of the A2B adenosine receptor in stimulation of adenylate cyclase, phospholipase Cβ, and interleukin-8

  • Sergey Ryzhov
  • Rinat Zaynagetdinov
  • Anna E. Goldstein
  • Anton Matafonov
  • Italo Biaggioni
  • Igor Feoktistov
Original Article

Abstract

In human mast cells and microvascular endothelial cells, the A2B adenosine receptor controls at least three independent signaling pathways, i.e., Gs-mediated stimulation of adenylate cyclase, Gq-mediated stimulation of phospholipase Cβ, and Gs/Gq-independent upregulation of IL-8. Functional analysis of cells transfected with full-length and truncated receptor constructs revealed that the A2B receptor C-terminus is important for coupling to Gs and Gq proteins. Removal of the entire cytoplasmic portion in the A2B receptor C-terminus rendered it incapable of stimulating adenylate cyclase and phospholipase Cβ. Conversely, removal of the distal 16 amino acids facilitated signal transduction from the receptor to the downstream Gs but not Gq proteins. However, the A2B receptor C-terminus is not essential for upregulation of IL-8. Analysis of chimeric A2A/A2B receptors demonstrated that only chimeras containing the third intracellular loop of the A2B receptor mediated agonist-dependent IL-8 reporter stimulation, suggesting that this domain is important for upregulation of IL-8.

Keywords

Adenosine Purinergic receptors P1 Interleukin-8 Adenylate cyclase Type C phospholipases GTP-binding proteins 

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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Sergey Ryzhov
    • 1
  • Rinat Zaynagetdinov
    • 1
  • Anna E. Goldstein
    • 2
  • Anton Matafonov
    • 1
  • Italo Biaggioni
    • 3
  • Igor Feoktistov
    • 4
    • 5
  1. 1.Division of Cardiovascular Medicine, Department of MedicineVanderbilt UniversityNashvilleUSA
  2. 2.Division of Clinical Pharmacology, Department of PharmacologyVanderbilt UniversityNashvilleUSA
  3. 3.Division of Clinical Pharmacology, Departments of Medicine and PharmacologyVanderbilt UniversityNashvilleUSA
  4. 4.Division of Cardiovascular Medicine, Departments of Medicine and PharmacologyVanderbilt UniversityNashvilleUSA
  5. 5.360 PRBVanderbilt UniversityNashvilleUSA

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