Characterization of adenosine receptors in human erythroleukemia cells and platelets: further evidence for heterogeneity of adenosine A2 receptor subtypes.
Characterization of adenosine receptors in human erythroleukemia cells and platelets: further evidence for heterogeneity of adenosine A2 receptor subtypes.
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发表时间：
1993-06
影响因子：
3.6
通讯作者：
I. Feoktistov;Italo Biaggioni
中科院分区：
文献类型：
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作者：
I. Feoktistov;Italo Biaggioni
腺苷受体存在于血小板中，它们的激活导致cAMP的积聚和聚集的抑制。然而，由于不可能在体外维持这些细胞，对血小板腺苷受体的研究受到限制。人红白血病(HEL)细胞表达巨核/血小板标志物，已被用作研究血小板受体的模型。因此，我们试图确定HEL细胞中是否存在腺苷受体。腺苷激动剂在HEL细胞中产生cAMP积聚，这意味着A2受体的存在。黄嘌呤和非黄嘌呤腺苷受体拮抗剂以一种简单的竞争性方式阻断这一效应(斯柴尔德分析)。因此，血小板和HEL细胞都具有A2腺苷受体。然而，它们之间存在着显著的差异。一般来说，腺苷激动剂在HEL细胞中的效力低于血小板。特别是，腺苷类似物CGS 21680是血小板中最有效的激动剂之一，在HEL细胞中几乎不起作用。激动剂的效价顺序为：5‘-N-乙基氨基腺苷(0.19微米)=CGS 21680(0.18微米)；(R)-(-)-N6-(2-苯基异丙基)腺苷(0.5微米)；5’-N-乙基氨基腺苷(2.4微米)>；(R)-(-)-N6-(2-苯基异丙基)腺苷(160微米)和GT；与激动剂在HEL细胞中的效力降低相反，拮抗剂1，3-二丙基-8-对磺基苯基黄嘌呤在HEL细胞中的效力比在血小板中更强。根据激动剂和拮抗剂的效价顺序的显著差异，我们认为HEL细胞和血小板具有不同的腺苷A2受体亚型。我们发现CGS 21680在区分这些受体亚型方面特别有帮助。
Adenosine receptors are present in platelets, and their activation results in accumulation of cAMP and inhibition of aggregation. The study of platelet adenosine receptors, however, is limited by the impossibility of maintaining these cells in vitro. Human erythroleukemia (HEL) cells express megakaryocytic/platelet markers and have been used as a model to study platelet receptors. Therefore, we sought to determine whether adenosine receptors were present in HEL cells. Adenosine agonists produced an accumulation of cAMP in HEL cells, implying the presence of A2 receptors. Xanthine and nonxanthine adenosine receptor antagonists blocked this effect in a simple competitive manner (Schild analysis). Therefore, both platelets and HEL cells possess A2 adenosine receptors. There were, however, significant differences between them. Adenosine agonists were, in general, less potent in HEL cells, compared with platelets. In particular, the adenosine analog CGS 21680, one of the most potent agonists in platelets, was virtually inactive in HEL cells. The orders of potencies for agonists (and their EC50 values for cAMP production) were 5'-N-ethylcarboxamidoadenosine (0.19 microM) = CGS 21680 (0.18 microM) > (R)-(-)-N6-(2-phenylisopropyl)adenosine (0.5 microM) in platelets and 5'-N-ethylcarboxamidoadenosine (2.4 microM) > (R)-(-)-N6-(2-phenylisopropyl)adenosine (160 microM) >> CGS 21680 (1600 microM) in HEL cells. In contrast to the decreased potency of agonists in HEL cells, the antagonist 1,3-dipropyl-8-p-sulfophenylxanthine was more potent in HEL cells, compared with platelets. Based on the striking differences in the rank orders of potencies of agonists and antagonists, we propose that HEL cells and platelets have different subtypes of adenosine A2 receptors. We found CGS 21680 particularly helpful in distinguishing between these receptor subtypes.