Abstract
Effect of novel adenosine A3 receptor antagonist SSR161421 in allergic sheep models
Highlights
Adenosine is thought to be an important pathological mediator in asthma
We recently showed that SSR161421 has significant in-vivo pharmacologic activity against adenosine A3 ligand specific and allergic disease models in rodents and guinea pigs [11,12]
To gain insight into this problem, we evaluated SSR161421, a new selective human adenosine A3 receptor antagonist, adenosine A3 receptor involvement in the antigen-induced responses in allergic sheep both in-vitro and in-vivo
Summary
Adenosine is thought to be an important pathological mediator in asthma. Adenosine evokes bronchoconstriction in airways by directly acting in bronchial smooth muscle cells or indirectly by inducing the release of mast cell mediators and by acting on airway afferent nerve endings [1,2,3,4].Allergen challenge increases the bronchial level of adenosine [5], which can affect mast cell function [6]. Adenosine evokes bronchoconstriction in airways by directly acting in bronchial smooth muscle cells or indirectly by inducing the release of mast cell mediators and by acting on airway afferent nerve endings [1,2,3,4]. The potential role of adenosine A3 receptor stimulation in the pathophysiology of asthma, led to the development of a novel adenosine A3 receptor selective antagonist SSR161421. We recently showed that SSR161421 has significant in-vivo pharmacologic activity against adenosine A3 ligand specific and allergic disease models in rodents and guinea pigs [11,12]. Mouse and guinea pig adenosine A3 receptors shows only 73% and 75 % identity with human adenosine A3 receptor sequence, respectively
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