A new chemical tool (C0036E08) supports the role of adenosine A(2B) receptors in mediating human mast cell activation.

Détails

ID Serval
serval:BIB_0969DADB0916
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A new chemical tool (C0036E08) supports the role of adenosine A(2B) receptors in mediating human mast cell activation.
Périodique
Biochemical Pharmacology
Auteur(s)
Buceta M., Domínguez E., Castro M., Brea J., Alvarez D., Barcala J., Valdés L., Alvarez-Calderón P., Domínguez F., Vidal B., Díaz J.L., Miralpeix M., Beleta J., Cadavid M.I., Loza M.I.
ISSN
1873-2968[electronic], 0006-2952[linking]
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
76
Numéro
7
Pages
912-921
Langue
anglais
Notes
Publication types: In Vitro ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
Adenosine/pharmacology, Adenosine-5'-(N-ethylcarboxamide)/pharmacology, Animals, Aorta, Thoracic/drug effects, Aorta, Thoracic/physiology, Bronchoalveolar Lavage Fluid/cytology, Bronchoalveolar Lavage Fluid/immunology, CHO Cells, Cell Line, Cricetinae, Cricetulus, Cyclic AMP/metabolism, Guinea Pigs, Histamine Release/drug effects, Humans, Male, Mast Cells/drug effects, Mast Cells/immunology, Pyrimidines/pharmacology, Rats, Rats, Sprague-Dawley, Receptors, Purinergic P1/antagonists & inhibitors, Receptors, Purinergic P1/immunology
Pubmed
Web of science
Création de la notice
16/06/2010 11:22
Dernière modification de la notice
20/08/2019 12:31
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