2-Chloro-N6-cyclopentyladenosine: a highly selective agonist at A1 adenosine receptors
2-Chloro-N6-cyclopentyladenosine: a highly selective agonist at A1 adenosine receptors
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2-氯-N6-环戊基腺苷：A1 腺苷受体的高度选择性激动剂
DOI：
10.1007/bf00175797
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
M. Grifantini
中科院分区：
文献类型：
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作者：
M. Lohse;K. Klotz;U. Schwabe;G. Cristalli;S. Vittori;M. Grifantini
摘要合成了一种潜在的A1腺苷受体高亲和力配体-氯- n6 -环戊基腺苷（CCPA）。CCPA抑制[3H]PIA与大鼠脑膜A1受体的结合，其ki值为0.4 nM，而母体化合物n6 -环戊基腺苷（CPA）的ki值为0.8 nM。[3H]NECA与大鼠纹状体膜A2受体的结合被抑制，ki值为3900 nM，表明CCPA具有近10000倍的a1选择性。CCPA抑制A1受体模型大鼠脂肪细胞膜腺苷酸环化酶活性，ic50值为33 nM；刺激人血小板膜腺苷酸环化酶活性，ec50值为3500 nM。100倍以上的a1选择性优于38倍的CPA选择性。因此，CCPA是A1腺苷受体的激动剂，其选择性比CPA高4倍，亲和力比CPA高2倍，选择性比标准A1受体激动剂r - n6 -苯异丙基腺苷（R-PIA）高得多。CCPA是迄今为止报道的对A1受体选择性最高的激动剂。
Summary2-Chloro-N6-cyclopentyladenosine (CCPA) was synthesized as a potential high affinity ligand for A1 adenosine receptors. Binding of [3H]PIA to A1 receptors of rat brain membranes was inhibited by CCPA with a Ki-value of 0.4 nM, compared to a Ki-value of 0.8 nM for the parent compound N6-cyclopentyladenosine (CPA). Binding of [3H]NECA to A2 receptors of rat striatal membranes was inhibited with a Ki-value of 3900 nM, demonstrating an almost 10,000-fold A1-selectivity of CCPA.CCPA inhibited the activity of rat fat cell membrane adenylate cyclase, a model for the A1 receptor, with an IC50-value of 33 nM, and it stimulated the adenylate cyclase activity of human platelet membranes with an EC50-value of 3500 nM. The more than 100-fold A1-selectivity compares favourably with a 38-fold selectivity of CPA. Thus, CCPA is an agonist at A1 adenosine receptors with a 4-fold higher selectivity and 2-fold higher affinity than CPA, and a considerably higher selectivity than the standard A1 receptor agonist R-N6-phenylisopropyladenosine (R-PIA). CCPA represents the agonist with the highest selectivity for A1 receptors reported so far.