Gerhardt C C, Leysen J E, Planta R J, Vreugdenhil E, Van Heerikhuizen H
Department of Biochemistry and Molecular Biology, Vrije Universiteit, Amsterdam, Netherlands.
Eur J Pharmacol. 1996 Sep 12;311(2-3):249-58. doi: 10.1016/0014-2999(96)00410-4.
A G-protein-coupled receptor (5-HT2Lym) resembling members of the 5-HT2 receptor subfamily was cloned from the mollusc Lymnaea stagnalis. Serotonin induces a concentration-dependent increase in intracellular inositol phospates in HEK293 cells expressing this receptor (EC50 = 114 nM). 5-HT2Lym differs from mammalian 5-HT2 receptors by the presence of a large amino-terminal region. This large domain appears to preclude an adequate level of expression of 5-HT2Lym in HEK293. Therefore, we constructed a cDNA encoding an amino-terminally truncated receptor (delta N-5-HT2Lym) that appeared to be much better expressed in HEK293 cells. delta N-5-HT2Lym-expressing cells exhibit a serotonin-induced stimulation of phosphatidylinositol bisphosphate hydrolysis (EC50 = 11.4 nM) and a high-affinity binding of the 5-HT2-selective antagonist [3H]mesulergine (Kd = 4 nM). Inhibition of this binding by several 5-HT2 antagonists and agonists revealed a pharmacological profile most closely resembling those of 5HT2Dro, 5-HT2B and 5-HT2C.
从软体动物椎实螺中克隆出一种类似于5-HT2受体亚家族成员的G蛋白偶联受体（5-HT2Lym）。血清素可使表达该受体的HEK293细胞内的肌醇磷酸酯呈浓度依赖性增加（半数有效浓度=114 nM）。5-HT2Lym与哺乳动物的5-HT2受体不同，它有一个大的氨基末端区域。这个大结构域似乎阻碍了5-HT2Lym在HEK293细胞中的充分表达。因此，我们构建了一个编码氨基末端截短受体（δN-5-HT2Lym）的cDNA，该受体在HEK293细胞中的表达似乎要好得多。表达δN-5-HT2Lym的细胞表现出血清素诱导的磷脂酰肌醇二磷酸水解刺激（半数有效浓度=11.4 nM）以及5-HT2选择性拮抗剂[3H]美舒麦角的高亲和力结合（解离常数=4 nM）。几种5-HT2拮抗剂和激动剂对这种结合的抑制作用显示出一种与5HT2Dro、5-HT2B和5-HT2C最为相似的药理学特征。
