Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase.
Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase.
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DOI：
10.1016/s0021-9258(19)49479-9
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发表时间：
1993-11
期刊：
影响因子：
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通讯作者：
J. Bard;J. Zgombick;N. Adham;P. Vaysse;T. Branchek;R. Weinshank
中科院分区：
文献类型：
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作者：
J. Bard;J. Zgombick;N. Adham;P. Vaysse;T. Branchek;R. Weinshank
从人类基因组和cDNA文库中分离出一个含内含子的编码新型人5-HT受体的基因，该基因具有针对腺苷酸环化酶刺激性果蝇5-HT受体基因5-HTdrol的跨膜区的探针。从瞬时转染的Cos-7细胞收获的膜显示出高亲和力（Kd = 8.5 nM）、可饱和（Bmax = 6.6 pmol/mg蛋白）的[3 H]5-HT结合。肾上腺素能配体取代特异性[3 H]5-HT结合的效力等级顺序为：5-羧酰胺色胺>甲硫替平>美替戈林> 5-HT > 8-羟基-2-（二正丙基氨基）四氢萘>舒马曲坦>酮色林>扎考必利。5-HT产生了剂量依赖性（EC 50 = 992 nM）刺激（约20倍）的cAMP在瞬时转染细胞的积累，这种反应被拮抗的非选择性5-HT拮抗剂甲硫氨酸。该基因的RNA主要在人脑和外周组织的子集（包括冠状动脉和胃肠道的几种组织）中检测到。该受体的分子生物学和药理学特性表明，它是一个新的5-羟色胺受体亚家族（5-HT 7）的第一个成员。第二信使耦合，和组织分布表明可能的身份5-HT受体介导的舒张反应，在某些孤立的血管。
An intron-containing gene encoding a novel human serotonin (5-HT) receptor was isolated from human genomic and cDNA libraries with probes directed to transmembrane regions of the adenylate cyclase stimulatory Drosophila serotonin receptor gene, 5-HTdrol. Membranes harvested from transiently transfected Cos-7 cells displayed high affinity (Kd = 8.5 nM), saturable (Bmax = 6.6 pmol/mg protein) [3H]5-HT binding. The rank order of potencies for serotonergic ligands to displace specific [3H]5-HT binding was: 5-carboxamido-tryptamine > methiothepin > metergoline > 5-HT > 8-hydroxy-2-(di-n-propylamino)tetralin > sumatriptan > ketanserin > zacopride. 5-HT produced a dose-dependent (EC50 = 992 nM) stimulation (approximately 20-fold) of cAMP accumulation in transiently transfected cells, and this response was antagonized by the nonselective 5-HT antagonist methiothepin. RNA for this gene was predominantly detected in the human brain and a subset of peripheral tissues including coronary artery and several tissues of the gastrointestinal tract. The molecular biological and pharmacological properties of this receptor suggest that it is the first member of a new serotonin receptor subfamily (5-HT7). The second messenger coupling, and tissue distribution indicate a possible identity to 5-HT receptors that mediate relaxant responses in certain isolated blood vessels.