Chang C S, Negishi M, Nakano T, Morizawa Y, Matsumura Y, Ichikawa A
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Prostaglandins. 1997 Feb;53(2):83-90. doi: 10.1016/s0090-6980(97)00003-8.
Recently, we cloned cDNAs for the prostacyclin receptor (IP) and the four mouse PGE receptor subtypes, EP1, EP2, EP3, and EP4, and established Chinese hamster ovary cells that stably express each receptor. We examined the agonist potency and selectivity of AFP-07, a 7,7-difluoroprostacyclin derivative, compared with widely used stable prostacyclin analogue, iloprost, using the cells expressing each cloned receptor. AFP-07 strongly displaced the [3H] iloprost binding to the IP receptor-expressing cell membranes, the half maximal concentration for the displacement being 3 nM, which was one order lower than that of iloprost. AFP-07 concentration-dependently stimulated cAMP formation in the IP-expressing cells, the half-maximal concentration for the stimulation being 10 pM, which was one order lower than that of iloprost. On the other hand, AFP-07 showed lower affinity for EP1, EP2, EP3, and EP4 than PGE2, but iloprost had the same affinity as PGE2 for the EP1, These results demonstrate that AFP-07 is a potent and highly selective agonist for the IP receptor.
最近，我们克隆了前列环素受体（IP）以及四种小鼠前列腺素E受体亚型（EP1、EP2、EP3和EP4）的cDNA，并建立了稳定表达每种受体的中国仓鼠卵巢细胞。我们使用表达每种克隆受体的细胞，检测了7,7-二氟前列环素衍生物AFP-07与广泛使用的稳定前列环素类似物伊洛前列素相比的激动剂效力和选择性。AFP-07强烈取代了[3H]伊洛前列素与表达IP受体的细胞膜的结合，取代的半数最大浓度为3 nM，比伊洛前列素低一个数量级。AFP-07在表达IP的细胞中浓度依赖性地刺激cAMP形成，刺激的半数最大浓度为10 pM，比伊洛前列素低一个数量级。另一方面，AFP-07对EP1、EP2、EP3和EP4的亲和力低于前列腺素E2，但伊洛前列素与前列腺素E2对EP1的亲和力相同。这些结果表明，AFP-07是一种对IP受体有效的高选择性激动剂。
