Julius D, MacDermott A B, Axel R, Jessell T M
Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Science. 1988 Jul 29;241(4865):558-64. doi: 10.1126/science.3399891.
Neurons that release serotonin as a neurotransmitter project to most regions of the central and peripheral nervous system and mediate diverse neural functions. The physiological effects of serotonin are initiated by the activation of multiple, distinct receptor subtypes. Cloning in RNA expression vectors was combined with a sensitive electrophysiological assay in Xenopus oocytes in order to isolate a functional cDNA clone encoding the 5HTlc serotonin receptor. Injection of RNA transcribed in vitro from this clone into Xenopus oocytes elicits serotonin sensitivity. Mouse fibroblasts transformed with this clone bind serotonin agonists and antagonists and exhibit an increase in intracellular Ca2+ concentrations in response to serotonin. The sequence of the 5HTlc receptor reveals that it belongs to the family of G protein-coupled receptors, which are thought to traverse the cytoplasmic membrane seven times. Moreover, in situ hybridization and RNA blot analysis indicate that the 5HTlc receptor is expressed in neurons in many regions of the central nervous system and suggest that this subclass of receptor may mediate many of the central actions of serotonin.
释放血清素作为神经递质的神经元投射到中枢神经系统和外周神经系统的大部分区域，并介导多种神经功能。血清素的生理效应是由多种不同受体亚型的激活引发的。将RNA表达载体中的克隆与非洲爪蟾卵母细胞中的灵敏电生理测定相结合，以分离编码5HTlc血清素受体的功能性cDNA克隆。将从该克隆体外转录的RNA注射到非洲爪蟾卵母细胞中可引发血清素敏感性。用该克隆转化的小鼠成纤维细胞结合血清素激动剂和拮抗剂，并在对血清素的反应中表现出细胞内Ca2+浓度的增加。5HTlc受体的序列显示它属于G蛋白偶联受体家族，该家族被认为跨细胞质膜七次。此外，原位杂交和RNA印迹分析表明5HTlc受体在中枢神经系统许多区域的神经元中表达，并表明该受体亚类可能介导血清素的许多中枢作用。
