Comparison of the potency of adenosine as an agonist at human adenosine receptors expressed in Chinese hamster ovary cells
Comparison of the potency of adenosine as an agonist at human adenosine receptors expressed in Chinese hamster ovary cells
复制标题
DOI：
10.1016/s0006-2952(00)00570-0
复制
发表时间：
2001-02-15
影响因子：
5.8
通讯作者：
Schulte, G
中科院分区：
文献类型：
--
作者：
Fredholm, BB;Irenius, E;Schulte, G
使用稳定转染人 A(1)、A(2A)、A(2B) 和 A(3) 受体的完整中国仓鼠卵巢 (CHO) 细胞中环 AMP (cAMP) 形成的变化，通过功能测定检查腺苷和肌苷作为人腺苷受体激动剂的效力。腺苷增加表达 A(2A) (Ec(50): 0.7 muM) 和 A(2B) (Ec(50): 24 muM) 受体的细胞中的 cAMP 形成，并抑制毛喉素 (0.3-3 muM) 刺激的表达 A(1) (Ec(50): 0.7 muM) 和 A(3) 受体的细胞中的 cAMP 形成 (Ec(50): 0.29μM）。摄取抑制剂硝基苄基硫代肌苷 (NBMPR) 的存在不会改变腺苷对 A(2A) 和 A(2B) 受体的效力，而 NBMPR 对 A(1) 和 A(3) 受体的腺苷效力增加约 h 倍。在存在 NBMPR 的情况下，肌苷是一种有效的激动剂（Ec(50)：对于 A(1) 和 A(3) 受体分别为 7 和 0.08 muM），但功效较低，尤其是对于 A(3) 受体。肌苷对 A(2) 受体没有作用。咖啡因、茶碱和副黄嘌呤改变了腺苷在 A(1)、A(2A) 和 A(2B) 受体上的剂量反应曲线。这些结果表明，腺苷是所有人类腺苷受体的内源性激动剂，并且该核苷的生理水平可以激活细胞上大量表达的 A(1)、A(2A) 和 A(3) 受体，而需要病理生理条件才能刺激 A(2B) 受体产生环 AMP。 (C) 2001 Elsevier Science Inc. 保留所有权利。
The potency of adenosine and inosine as agonists at human adenosine receptors was examined in a functional assay using changes in cyclic AMP (cAMP) formation in intact Chinese hamster ovary (CHO) cells stably transfected with the human A(1), A(2A), A(2B), and A(3) receptors. Adenosine increased cAMP formation in cells expressing the A(2A) (Ec(50): 0.7 muM) and A(2B) (Ec(50): 24 muM) receptors and inhibited forskolin (0.3-3 muM)-stimulated cAMP formation in cells expressing the A(1) (Ec(50): 0.7 muM) and A(3) receptors (Ec(50): 0.29 muM). The potency of adenosine at the A(2A) and A(2B) receptors was not altered by the presence of the uptake inhibitor nitrobenzylthioinosine (NBMPR), whereas it was increased about h-fold by NBMPR at the A(1) and A(3) receptors. In the presence of NBMPR, inosine was a potent agonist (Ec(50): 7 and 0.08 muM at the A(1) and A(3) receptors, respectively), but with low efficacy especially at the A(3) receptors. No effect of inosine was seen at the A(2) receptors. Caffeine, theophylline, and paraxanthine shifted the dose-response curve for adenosine at the A(1), A(2A), and A(2B) receptors. These results indicate that adenosine is the endogenous agonist at all human adenosine receptors and that physiological levels of this nucleoside can activate A(1), A(2A), and A(3) receptors on cells where they are abundantly expressed, whereas pathophysiological conditions are required to stimulate A(2B) receptors to produce cyclic AMP. (C) 2001 Elsevier Science Inc. All rights reserved.