Activation of murine lung mast cells by the adenosine A3 receptor.
Adenosine has been implicated to play a role in asthma in part through its ability to influence mediator release from mast cells. Most physiological roles of adenosine are mediated through adenosine receptors; however, the mechanisms by which adenosine influences mediator release from lung mast cells are not understood. We established primary murine lung mast cell cultures and used real-time RT-PCR and immunofluorescence to demonstrate that the A(2A), A(2B), and A(3) adenosine receptors are expressed on murine lung mast cells. Studies using selective adenosine receptor agonists and antagonists suggested that activation of A(3) receptors could induce mast cell histamine release in association with increases in intracellular Ca(2+) that were mediated through G(i) and phosphoinositide 3-kinase signaling pathways. The function of A(3) receptors in vivo was tested by exposing mice to the A(3) receptor agonist, IB-MECA. Nebulized IB-MECA directly induced lung mast cell degranulation in wild-type mice while having no effect in A(3) receptor knockout mice. Furthermore, studies using adenosine deaminase knockout mice suggested that elevated endogenous adenosine induced lung mast cell degranulation by engaging A(3) receptors. These results demonstrate that the A(3) adenosine receptor plays an important role in adenosine-mediated murine lung mast cell degranulation.
Zhong
Hongyan
H
Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, TX 77030, USA.
Shlykov
Sergiy G
SG
Molina
Jose G
JG
Sanborn
Barbara M
BM
Jacobson
Marlene A
MA
Tilley
Stephen L
SL
Blackburn
Michael R
MR
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000243:Adenosine Deaminase / Q000172:deficiency / Q000235:genetics; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors; D006633:Histamine Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D008407:Mast Cells / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009330:Nebulizers and Vaporizers; D037342:Pertussis Toxin / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1 / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
D000241:Adenosine; D000243:Adenosine Deaminase; D002118:Calcium; D004791:Enzyme Inhibitors; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D006633:Histamine Antagonists; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine