Interaction of SSR161421, a novel specific adenosine A3 receptor antagonist with adenosine A3 receptor agonists both in vitro and in vivo

Mikus, Endre G.; Boer, Kinga; Timári, Géza; Urban-Szabo, Katalin; Kapui, Zoltán; Szeredi, Judit; Gerber, Katalin; Bátori, Sándor; Finet, M.; Arányi, Péter; Galzin, Anne-Marie

doi:10.1016/j.ejphar.2012.11.046

Cited by 4 publications

(2 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The potential role of adenosine A 3 receptor stimulation in the pathophysiology of asthma, led to the development of a novel adenosine A 3 receptor selective antagonist SSR161421. SSR161421 is a nanomolar adenosine A 3 receptor antagonist with at least three log selectivity towards other adenosine receptors (A 1 , A 2a , A 2b ) and adenosine unrelated molecular targets [11]. We recently showed that SSR161421 has significant in-vivo pharmacologic activity against adenosine A 3 ligand specific and allergic disease models in rodents and guinea pigs [11,12].…”

Section: Introductionmentioning

confidence: 99%

“…SSR161421 is a nanomolar adenosine A 3 receptor antagonist with at least three log selectivity towards other adenosine receptors (A 1 , A 2a , A 2b ) and adenosine unrelated molecular targets [11]. We recently showed that SSR161421 has significant in-vivo pharmacologic activity against adenosine A 3 ligand specific and allergic disease models in rodents and guinea pigs [11,12]. However, mouse and guinea pig adenosine A 3 receptors shows only 73% and 75 % identity with human adenosine A 3 receptor sequence, respectively.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of novel adenosine A3 receptor antagonist SSR161421 in allergic sheep models

Mikus¹,

Arányi²,

Boer³

et al. 2016

Pulm Crit Care Med

Self Cite

View full text Add to dashboard Cite

Sheep is a species that shows 85% overall identity of the adenosine A 3 receptor with its human ortholog. In this study we demonstrate a role for the adenosine A3 receptor in ovine allergic airway responses. In isolated tracheal preparations taken from sheep naturally sensitive to Ascaris suum, antigen challenge evoked airway smooth muscle contraction. The smooth muscle contractile response was dependent on the applied Ascaris suum antigen dose. The response to a threshold dose of antigen was enhanced in the presence of an adenosine A3 agonist AB-MECA (10-6M), suggesting that adenosine A3 receptor function contributed to the enhanced allergen response. This was confirmed by showing that a selective adenosine A 3 receptor antagonist SSR16142, inhibited the increased antigen response with EC 50 =2•10 -9 M. We then tested the effects of SSR161421, given intravenously, on antigen-induced responses in allergic sheep following inhalation of Ascaris suum, in-vivo. SSR161421 (0.3-3 mg/kg) provided dose-dependent inhibition of the antigen-induced late bronchoconstrictor responses and the post antigen-induced airway hyper responsiveness. This is the first demonstration that a selective adenosine A 3 receptor antagonist inhibits antigen-induced responses in a species with an A3 receptor that bears significant similarity to its human counterpart.

show abstract

Section: Introductionmentioning

confidence: 99%