title: A new chemical tool (C0036E08) supports the role of adenosine A(2B) receptors in mediating human mast cell activation.
abstract: Asthma is a chronic inflammatory disease of the airways that involves many cell types, amongst which mast cells are known to be important. Adenosine, a potent bronchoconstricting agent, exerts its ability to modulate adenosine receptors of mast cells thereby potentiating derived mediator release, histamine being one of the first mediators to be released. The heterogeneity of sources of mast cells and the lack of highly potent ligands selective for the different adenosine receptor subtypes have been important hurdles in this area of research. In the present study we describe compound C0036E08, a novel ligand that has high affinity (pK(i) 8.46) for adenosine A(2B) receptors, being 9 times, 1412 times and 3090 times more selective for A(2B) receptors than for A(1), A(2A) and A(3) receptors, respectively. Compound C0036E08 showed antagonist activity at recombinant and native adenosine receptors, and it was able to fully block NECA-induced histamine release in freshly isolated mast cells from human bronchoalveolar fluid. C0036E08 has been shown to be a valuable tool for the identification of adenosine A(2B) receptors as the adenosine receptors responsible for the NECA-induced response in human mast cells. Considering the increasing interest of A(2B) receptors as a therapeutic target in asthma, this chemical tool might provide a base for the development of new anti-asthmatic drugs.
authors.affiliation: BioFarma Research Group, Department of Pharmacology, School of Pharmacy, Instituto de Farmacia Industrial, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Buceta
authors.forename: Eduardo
authors.initials: E
authors.lastname: Domínguez
authors.forename: Marián
authors.initials: M
authors.lastname: Castro
authors.forename: José
authors.initials: J
authors.lastname: Brea
authors.forename: David
authors.initials: D
authors.lastname: Alvarez
authors.forename: Javier
authors.initials: J
authors.lastname: Barcala
authors.forename: Luis
authors.initials: L
authors.lastname: Valdés
authors.forename: Pedro
authors.initials: P
authors.lastname: Alvarez-Calderón
authors.forename: Fernando
authors.initials: F
authors.lastname: Domínguez
authors.forename: Bernat
authors.initials: B
authors.lastname: Vidal
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Díaz
authors.forename: Montse
authors.initials: M
authors.lastname: Miralpeix
authors.forename: Jorge
authors.initials: J
authors.lastname: Beleta
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Cadavid
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Loza
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000276:immunology / Q000378:metabolism
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D018047:Receptors, Purinergic P1; D019830:Adenosine-5'-(N-ethylcarboxamide); D000242:Cyclic AMP; D000241:Adenosine