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Research Article Free access | 10.1172/JCI119833

Inosine binds to A3 adenosine receptors and stimulates mast cell degranulation.

X Jin, R K Shepherd, B R Duling, and J Linden

Department of Biochemistry, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.

Find articles by Jin, X. in: JCI | PubMed | Google Scholar

Department of Biochemistry, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.

Find articles by Shepherd, R. in: JCI | PubMed | Google Scholar

Department of Biochemistry, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.

Find articles by Duling, B. in: JCI | PubMed | Google Scholar

Department of Biochemistry, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.

Find articles by Linden, J. in: JCI | PubMed | Google Scholar

Published December 1, 1997 - More info

Published in Volume 100, Issue 11 on December 1, 1997
J Clin Invest. 1997;100(11):2849–2857. https://doi.org/10.1172/JCI119833.
© 1997 The American Society for Clinical Investigation
Published December 1, 1997 - Version history
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Abstract

We investigated the mechanism by which inosine, a metabolite of adenosine that accumulates to > 1 mM levels in ischemic tissues, triggers mast cell degranulation. Inosine was found to do the following: (a) compete for [125I]N6-aminobenzyladenosine binding to recombinant rat A3 adenosine receptors (A3AR) with an IC50 of 25+/-6 microM; (b) not bind to A1 or A2A ARs; (c) bind to newly identified A3ARs in guinea pig lung (IC50 = 15+/-4 microM); (d) lower cyclic AMP in HEK-293 cells expressing rat A3ARs (ED50 = 12+/-5 microM); (e) stimulate RBL-2H3 rat mast-like cell degranulation (ED50 = 2.3+/-0.9 microM); and (f) cause mast cell-dependent constriction of hamster cheek pouch arterioles that is attenuated by A3AR blockade. Inosine differs from adenosine in not activating A2AARs that dilate vascular smooth muscle and inhibit mast cell degranulation. The A3 selectivity of inosine may explain why it elicits a monophasic arteriolar constrictor response distinct from the multiphasic dilator/constrictor response to adenosine. Nucleoside accumulation and an increase in the ratio of inosine to adenosine may provide a physiologic stimulus for mast cell degranulation in ischemic or inflamed tissues.

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