Plassat J L, Boschert U, Amlaiky N, Hen R
Laboratoire de Génétique Moléculaire des Eukaryotes du CNRS, U/184 de Biologie Moléculaire et de Génie Génétique de l'INSERM, Strasbourg, France.
EMBO J. 1992 Dec;11(13):4779-86. doi: 10.1002/j.1460-2075.1992.tb05583.x.
Serotonin (5-HT) is a neuromodulator that mediates a wide range of physiological functions by activating multiple receptors. Using a strategy based on amino acid sequence homology between 5-HT receptors that interact with G proteins, we have isolated a cDNA encoding a new serotonin receptor from a mouse brain library. Amino acid sequence comparisons revealed that this receptor was a distant relative of all previously identified 5-HT receptors; we therefore named it 5HT5. When expressed in Cos-7 cells and NIH-3T3 cells, the 5HT5 receptor displayed a high affinity for the serotonergic radioligand [125I]LSD. Surprisingly, its pharmacological profile resembled that of the 5HT1D receptor, which is a 5-HT receptor subtype which has been shown to inhibit adenylate cyclase and which is predominantly expressed in basal ganglia. However, unlike 5HT1D receptors, the 5HT5 receptor did not inhibit adenylate cyclase and its mRNA was not found in basal ganglia. On the contrary, in situ hybridization experiments revealed that the 5HT5 mRNA was expressed predominantly in cerebral cortex, hippocampus, habenula, olfactory bulb and granular layer of the cerebellum. Our results therefore demonstrate that the 5HT1D receptors constitute a heterogeneous family of receptors with distinct intracellular signalling properties and expression patterns.
血清素（5-羟色胺，5-HT）是一种神经调质，通过激活多种受体介导广泛的生理功能。利用基于与G蛋白相互作用的5-HT受体之间氨基酸序列同源性的策略，我们从小鼠脑文库中分离出一个编码新型血清素受体的cDNA。氨基酸序列比较显示，该受体是所有先前鉴定的5-HT受体的远亲；因此我们将其命名为5HT5。当在Cos-7细胞和NIH-3T3细胞中表达时，5HT5受体对血清素能放射性配体[125I]麦角酸二乙胺（LSD）表现出高亲和力。令人惊讶的是，其药理学特征类似于5HT1D受体，5HT1D受体是一种5-HT受体亚型，已被证明可抑制腺苷酸环化酶，且主要在基底神经节中表达。然而，与5HT1D受体不同，5HT5受体不抑制腺苷酸环化酶，且在基底神经节中未发现其mRNA。相反，原位杂交实验表明，5HT5 mRNA主要在大脑皮质、海马、缰核、嗅球和小脑颗粒层中表达。因此，我们的结果表明，5HT1D受体构成了一个具有不同细胞内信号特性和表达模式的异质性受体家族。
