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

详细信息    查看全文

• 作者：Endre G. Mikus ; ^{endre.mikus@labmagister.com} ; Kinga Boé ; r ; Gé ; za Timá ; ri ; Katalin Urbá ; n-Szabó ; Zoltá ; n Kapui ; Judit Szeredi ; Katalin Gerber ; Tibor Szabó ; Sá ; ndor Bá ; tori ; Michel Finet ; Pé ; ter Ará ; nyi ; Anne-Marie Galzin
• 关键词：Human adenosine A3 receptors ; Adenosine A3 receptor antagonist ; Ear oedema ; Histamine release
• 刊名：European Journal of Pharmacology
• 出版年：2013
• 出版时间：15 January, 2013
• 年：2013
• 卷：699
• 期：1-3
• 页码：62-66
• 全文大小：230 K

文摘

A novel adenosine A₃ receptor antagonist (SSR161421) was characterized by both receptor binding assays and pharmacological tests. Binding studies on cloned human adenosine receptors showed that SSR161421 has high affinity for adenosine hA₃ receptors (K_i=0.37 nM) with at least 1000-fold selectivity compared to hA₁, hA_2A and hA_2B receptors. The receptor antagonist nature of SSR161421 was determined in a functional study on Chinese hamster ovarian cells (CHO) cells expressing human adenosine A₃ receptors. SSR161421 competitively antagonized the effect of 2-chloro-N6-(3-iodobenzyl)-adenosine-5¡ä-N-methylcarboxamide (Cl-IB-MECA) on cAMP production with a pA2 value in a luciferase reporter gene construct. In mice, intravenously administered SSR161421 inhibited the N6-(4-aminobenzyl)-adenosine-5¡ä-N-methyl-uronamide dihydrochloride (AB-MECA) induced increase in plasma histamine levels (ED₅₀=2.0 mg/kg) and the Cl-IB-MECA evoked plasma extravasation (ID₅₀=2.9 mg/kg) and oedema formation (ID₅₀=4.6 mg/kg) in mouse ear.