MRS 1754 is a selective A2B adenosine receptor antagonist [1]. MRS 1754 blocks adenosine binding to the A2B receptor, thereby inhibiting downstream signaling pathways mediated by the receptor (e.g., cAMP production and inflammatory cytokine release) [2]. MRS 1754 is commonly used in asthma and chronic obstructive pulmonary disease research [3-4].
In rat aortic vascular smooth muscle cells, MRS 1754 (0.1μM; 4d) significantly attenuated the decrease in [3H]thymidine incorporation induced by 2′,3′-cAMP [5]. In preglomerular vascular smooth muscle cells, MRS-1754 (100nM; 4d) inhibited the antiproliferative effect of adenosine [6].
In cecal ligation and puncture-induced sepsis mice model, MRS 1754 (0.5-10mg/kg; sc; 3d) treatment significantly improved the survival rate of mice [7]. In gut ischemia and reperfusion mice model, MRS 1754 (9.52μM/kg; iv; single injection) blocks A2B-type adenosine receptors, counteracting the protective effects of NECA on leukocyte-endothelial interactions and capillary perfusion [8].
References:
[1]. Ji X, Kim Y C, Ahern D G, et al. [3H] MRS 1754, a selective antagonist radioligand for A2B adenosine receptors[J]. Biochemical pharmacology, 2001, 61(6): 657-663.
[2]. Fogli E. Adenosine receptors modulation of inflammatory cells: the foam cells history[J]. 2010.
[3]. Haskó G, Linden J, Cronstein B, et al. Adenosine receptors: therapeutic aspects for inflammatory and immune diseases[J]. Nature reviews Drug discovery, 2008, 7(9): 759-770.
[4]. Fozard J R, Tigani B, Wolber C, et al. Modeling the response of the asthmatic airways to adenosine: Mechanisms and receptors[J]. Drug development research, 2003, 59(1): 23-29.
[5]. Jackson E K, Ren J, Gillespie D G. 2′, 3′-cAMP, 3′-AMP, and 2′-AMP inhibit human aortic and coronary vascular smooth muscle cell proliferation via A2B receptors[J]. American Journal of Physiology-Heart and Circulatory Physiology, 2011, 301(2): H391-H401.
[6]. Jackson E K, Gillespie D G, Dubey R K. 2′-AMP and 3′-AMP inhibit proliferation of preglomerular vascular smooth muscle cells and glomerular mesangial cells via A2B receptors[J]. The Journal of pharmacology and experimental therapeutics, 2011, 337(2): 444-450.
[7]. Belikoff B G, Hatfield S, Georgiev P, et al. A2B adenosine receptor blockade enhances macrophage-mediated bacterial phagocytosis and improves polymicrobial sepsis survival in mice[J]. The Journal of Immunology, 2011, 186(4): 2444-2453.
[8]. Zhou J, Zimmermann K, Krieg T, et al. Adenosine receptor activation improves microcirculation in experimental intestinal ischemia/reperfusion[J]. Clinical Hemorheology and Microcirculation, 2015, 59(3): 257-265.
MRS 1754是一种选择性A2B腺苷受体拮抗剂 [1]。MRS 1754阻断腺苷与A2B受体结合，从而抑制该受体介导的下游信号通路（例如cAMP生成和炎症细胞因子释放） [2]。MRS 1754常用于哮喘和慢性阻塞性肺病的研究 [3-4]。
在大鼠主动脉血管平滑肌细胞中，MRS 1754（0.1μM；4d）显著减弱了2′,3′-cAMP诱导的[3H]胸苷掺入的减少 [5]。在肾小球前血管平滑肌细胞中，MRS-1754（100nM；4d）抑制了腺苷的抗增殖作用 [6]。
在盲肠结扎穿刺诱发的脓毒症小鼠模型中，MRS 1754（0.5-10mg/kg；sc；3d）治疗显著提高了小鼠的存活率 [7]。在肠缺血再灌注小鼠模型中，MRS 1754（9.52μM/kg；iv；单次注射）阻断了A2B型腺苷受体，从而抵消了NECA对白细胞-内皮细胞相互作用和毛细血管灌注的保护作用 [8]。