Adham N, Kao H T, Schecter L E, Bard J, Olsen M, Urquhart D, Durkin M, Hartig P R, Weinshank R L, Branchek T A
Synaptic Pharmaceutical Corporation, Paramus, NJ 07652.
Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):408-12. doi: 10.1073/pnas.90.2.408.
An intronless gene encoding an additional human serotonin (5-HT) 5-HT1-like receptor subtype was isolated from a human genomic library with probes obtained from degenerate PCR primers used to amplify 5-HT-receptor-specific sequences. The highest degree of homology was found with the 5-HT1E subtype (70%) and the 5-HT1D alpha (63%) and 5-HT1D beta (60%) receptors. RNA for this gene was detected in the human brain but was not detected in kidney, liver, spleen, heart, pancreas, and testes. High-affinity (Kd = 9.2 nM) 3H-labeled 5-HT binding was detected. Competition studies revealed the following rank order of potencies for serotonergic ligands: 5-HT > sumatriptan >> 5-carboxyamidotryptamine > 8-hydroxy-2(di-1-propylamino)tetralin > spiperone. 5-HT produced a dose-dependent inhibition of forskolin-stimulated cAMP accumulation (EC50 = 7.9 nM) in transfected cells. These properties distinguish this receptor from any previously characterized and establish a fifth 5-HT1-like receptor subtype (5-HT1F) coupled to the inhibition of adenylate cyclase.
利用从用于扩增5-羟色胺（5-HT）受体特异性序列的简并PCR引物获得的探针，从人基因组文库中分离出一个无内含子基因，该基因编码另一种人5-HT 5-HT1样受体亚型。发现该基因与5-HT1E亚型（70%）、5-HT1Dα（63%）和5-HT1Dβ（60%）受体具有最高程度的同源性。在人脑中检测到了该基因的RNA，但在肾脏、肝脏、脾脏、心脏、胰腺和睾丸中未检测到。检测到高亲和力（Kd = 9.2 nM）的3H标记5-HT结合。竞争研究揭示了5-羟色胺能配体的效力顺序如下：5-HT > 舒马曲坦 >> 5-羧酰胺色胺 > 8-羟基-2（二-1-丙基氨基）四氢萘 > 螺哌隆。5-HT在转染细胞中对福司可林刺激的cAMP积累产生剂量依赖性抑制（EC50 = 7.9 nM）。这些特性将该受体与之前鉴定的任何受体区分开来，并确立了第五种与腺苷酸环化酶抑制偶联的5-HT1样受体亚型（5-HT1F）。
