克隆人类前列腺素受体与小说的特点,EP2子类型定义的药物。
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里根JW,贝利TJ Pepperl DJ,皮尔斯KL, Bogardus, Donello我,费尔贝恩CE、[1公里,伍德沃德DF,吉尔DW
克隆人类前列腺素受体与小说的特点,EP2子类型定义的药物。
摩尔杂志。1994年8月,46 (2):213 - 20。
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8078484 (在PubMed]
- 文摘
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cDNA表达,当定义的绑定和功能特性药物EP2前列腺素(PG)受体(Cardiovasc。药物启11:165 - 179(1993))已经从人类胎盘克隆库。这个克隆,被称为Hup-4,编码358个氨基酸的蛋白质,只有大约30%的整体的身份与其他PG受体,包括老鼠和人类克隆被指定为EP2受体研究[J。医学杂志。化学268:7759 - 7762 (1993);物化学。Biophys。Commun >, 197:263 - 270 (1993)]。与Hup-4 COS-7细胞转染,PGE2刺激阵营的EC50的形成大约50 nM。EP2-selective受体激动剂AH13205和butaprost也活跃,与EC50值在2 - 6 microM的范围。 The order of potency of PGs for competition with binding of [3H]PGE2 to membranes prepared from COS-7 cells transfected with Hup-4 was PGE2 > or = PGE1 > 16,16-dimethyl-PGE2 > or = 11-deoxy-PGE1 > butaprost > AH13205 > 19(R)-OH-PGE2. Natural PGs and analogues that are selective for the FP (PGF2a), DP (PGD2), EP1 (sulprostone), EP3 (MB 28767), and EP4 (1-OH-PGE1) receptors were inactive or competed poorly with the binding of [3H]PGE2 (< 50% displacement of specific binding at 10 microM). Northern blot analysis showed the presence of a Hup-4 message of approximately 3.1 kilobases in mRNA from human lung and placenta. Reverse transcription-polymerase chain reaction studies also indicated that Hup-4 is probably expressed in human uterus and in HL-60 (human promyelocytic leukemia) cells. Our findings suggest that Hup-4 encodes the pharmacologically defined EP2 receptor, whereas the mouse and human cDNAs previously classified as EP2 may represent another EP receptor subtype or the recently defined EP4 subtype [Prostaglandins 47:151-168 (1994)].