Adenosine A 3 receptors promote degranulation of rat mast cells both in vitro and in vivo

Reeves, J.J.; Jones, Caitlin A.; Sheehan, Michael J.; Vardey, C.J.; Whelan, C. J.

doi:10.1007/s000110050169

Cited by 72 publications

(58 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our studies show that plasma protein extravasation in response to adenosine is mediated entirely through activation of the A 3 receptor, as adenosine cannot provoke this physiological response in mice lacking this receptor. These findings are consistent with reports showing that pharmacologic reagents that preferentially bind to the A 3 receptor are effective at inducing edema formation (30,38).…”

Section: Discussionsupporting

confidence: 93%

See 1 more Smart Citation

Adenosine and inosine increase cutaneous vasopermeability by activating A3 receptors on mast cells

Tilley¹,

Wagoner²,

Salvatore³

et al. 2000

J. Clin. Invest.

177

141

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 93%

“…Nevertheless, most studies suggest that A 2B and A 3 receptors are predominantly involved (24)(25)(26)(27)(28)(29)(30)(31)(32). The differential importance assigned to these receptors in mast-cell degranulation may reflect the fact that mast cells examined were from different species and tissues.…”

Section: Introductionmentioning

confidence: 99%

Adenosine and inosine increase cutaneous vasopermeability by activating A3 receptors on mast cells

Tilley¹,

Wagoner²,

Salvatore³

et al. 2000

J. Clin. Invest.

177

141

View full text Add to dashboard Cite

“…This effect of adenosine on preformed mediator release is mediated by A 3 adenosine receptors in rodents (23,(41)(42)(43), but perhaps not in human (44) or canine (45) mast cells. We found that an enhanced Ag-induced degranulation in A 2B KO BMMCs was observed both in the absence and presence of the adenosine receptor agonist NECA, but the degree of potentiation mediated via A 3 receptors was essentially the same as in WT cells.…”

Section: Discussionmentioning

confidence: 95%

Effect of A2B Adenosine Receptor Gene Ablation on Proinflammatory Adenosine Signaling in Mast Cells

Ryzhov¹,

Zaynagetdinov²,

Goldstein

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

We have previously shown that A2B adenosine receptors (AR) play a pro‐inflammatory/pro‐angiogenic role, upregulating production of Th2 cytokines and angiogenic factors in human HMC‐1 mast cells.1,2 However, the pro‐inflammatory role of A2bAR in mast cells was recently questioned by a study that found an enhanced antigen‐induced degranulation of A2bAR knockout (A2BKO) mouse bone marrow‐derived mast cells (BMMCs).3 The authors interpreted this as evidence of anti‐inflammatory actions of A2BAR in BMMCs and suggested that A2BAR antagonists with inverse agonist activity could promote activation of mast cells. Here, we revisited these conclusions by studying the effect of genetic A2BAR ablation on adenosine‐dependent regulation of BMMCs. Our results show that genetic ablation of A2BAR had no effect on adenosine‐dependent potentiation of antigen‐induced degranulation, but abrogated adenosine‐dependent stimulation of IL‐13 and VEGF secretion. A2BAR antagonists with inverse agonist activity inhibited A2BAR‐dependent secretion, but did not mimic the enhanced antigen‐induced degranulation observed in A2BKO BMMCs. Thus, our study confirmed the pro‐inflammatory role of mast cell A2BAR and demonstrated anti‐inflammatory actions of A2BAR antagonists. Supported by NIH.

show abstract

“…Therefore, our results provide unequivocal evidence for a role of the A3R in mediating signaling provoked in HMCs undergoing inflammatory processes. Notably, although studies in rodent mast cells and rodent animal models have firmly established the central role played by the A3R in mediating inflammatory processes, including bronchoconstriction, hypotension, and cutaneous allergic reactions (23)(24)(25)(26), the role of the A3R in humans remained controversial. The literature split between reports revealing proinflammatory functions of the A3R, as opposed to evidence demonstrating anti-inflammatory and protective outcomes have led Gessi et al to coin the A3R as the "Dr. Jekyll and Mr. Hyde" of the inflammatory reaction (27).…”

Section: Discussionmentioning

confidence: 99%

Activation of Mast Cells by Trimeric G Protein Gi3; Coupling to the A3 Adenosine Receptor Directly and upon T Cell Contact

Baram

Dekel

Mekori

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

Mast cells are key players in mediating and amplifying allergic and inflammatory reactions. Previously, we identified the G-protein, Gi3, as the cellular target of receptor mimetic basic secretagogues that activate mast cell independently of IgE. In this study, we demonstrate that Gi3 is the cellular target of the adenosine A3 receptor (A3R), a G-protein coupled receptor involved in inflammation and the pathophysiology of asthma. By using a cell permeable peptide comprising the C-terminal end of Gαi3 fused to an importation sequence (ALL1) as a selective inhibitor of Gi3 signaling, we show that by coupling to Gi3, the A3R stimulates multiple signaling pathways in human mast cells, leading to upregulation of cytokines, chemokines, and growth factors. We further show that after contact with activated T cell membranes, endogenous adenosine binds to and activates the A3R, resulting in Gi3-mediated signaling. Specifically, the majority of ERK1/2 signaling initiated by contact with activated T cell membranes, is mediated by Gi3, giving rise to ALL1-inhibitable cellular responses. These results unveil the physiological G-protein coupled receptor that couples to Gi3 and establish the important role played by this G-protein in inflammatory conditions that involve adenosine-activated mast cells.

show abstract

Adenosine A 3 receptors promote degranulation of rat mast cells both in vitro and in vivo

Abstract: These results indicate that stimulation of adenosine A3 receptors both enhances degranulation in vitro and directly produces degranulation of rat mast cells in vivo.

Cited by 72 publications

References 14 publications

Adenosine and inosine increase cutaneous vasopermeability by activating A3 receptors on mast cells

Adenosine and inosine increase cutaneous vasopermeability by activating A3 receptors on mast cells

Effect of A2B Adenosine Receptor Gene Ablation on Proinflammatory Adenosine Signaling in Mast Cells

Activation of Mast Cells by Trimeric G Protein Gi3; Coupling to the A3 Adenosine Receptor Directly and upon T Cell Contact

Contact Info

Product

Resources

About