Adenosine and inosine increase cutaneous vasopermeability by activating A(3) receptors on mast cells.
Adenosine has potent effects on both the cardiovascular and immune systems. Exposure of tissues to adenosine results in increased vascular permeability and extravasation of serum proteins. The mechanism by which adenosine brings about these physiological changes is poorly defined. Using mice deficient in the A(3) adenosine receptor (A(3)AR), we show that increases in cutaneous vascular permeability observed after treatment with adenosine or its principal metabolite inosine are mediated through the A(3)AR. Adenosine fails to increase vascular permeability in mast cell-deficient mice, suggesting that this tissue response to adenosine is mast cell-dependent. Furthermore, this response is independent of activation of the high-affinity IgE receptor (FcepsilonR1) by antigen, as adenosine is equally effective in mediating these changes in FcepsilonR1 beta-chain-deficient mice. Together these results support a model in which adenosine and inosine induce changes in vascular permeability indirectly by activating mast cells, which in turn release vasoactive substances. The demonstration in vivo that adenosine, acting through a specific receptor, can provoke degranulation of this important tissue-based effector cell, independent of antigen activation of the high-affinity IgE receptor, supports an important role for this nucleoside in modifying the inflammatory response.
Tilley
S L
SL
Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Wagoner
V A
VA
Salvatore
C A
CA
Jacobson
M A
MA
Koller
B H
BH
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D007288:Inosine / Q000494:pharmacology*; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D043684:Receptor, Adenosine A3; D017455:Receptors, IgE / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000098:blood supply* / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology*
D043684:Receptor, Adenosine A3; D017455:Receptors, IgE; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D007288:Inosine; D000241:Adenosine