Flor P J, Van Der Putten H, Rüegg D, Lukic S, Leonhardt T, Bence M, Sansig G, Knöpfel T, Kuhn R
CNS Research, Ciba, CH-4002 Basle, Switzerland.
Neuropharmacology. 1997 Feb;36(2):153-9. doi: 10.1016/s0028-3908(96)00176-1.
Two splice variants of the human metabotropic glutamate receptor 7, named hmGluR7a and hmGluR7b, were isolated from a human brain cDNA library. The isoforms differ by an out-of-frame insertion of 92 nucleotides close to the C-terminus of the hmGluR7 coding region, hmGluR7a has a length of 915 amino acids and represents the human homolog of the recently cloned rat mGluR7. hmGluR7b is seven amino acids longer and exhibits a novel C-terminus of 23 amino acids in length. RT-PCR analysis demonstrated the existence of mGluR7b transcripts in wild-type mouse brain and its absence in mGluR7 knockout mice. Northern blot analysis indicate that mGluR7 expression is developmentally regulated. It is expressed at high levels in human fetal brain and at a lower level in many regions of adult human brain. Stimulation of hmGluR7b with L-2-amino-4-phosphonobutyrate (L-AP4), L-serine-O-phosphate (L-SOP) or L-glutamate in stably transfected Chinese hamster ovary (CHO) cells depressed forskolin-induced cAMP accumulation, whereas (1S,3R)-1-aminocyclopentane-1,3,-dicarboxylic acid ((1S,3R)-ACPD) and quisqualate (both at 1mM) had no significant effects. As described for rat mGluR7, the rank order of agonist potencies is: L-SOP, L-AP4 > L-glutamate > (1S,3R)-ACPD, quisqualate.
从人脑海马cDNA文库中分离出了人代谢型谷氨酸受体7的两种剪接变体，分别命名为hmGluR7a和hmGluR7b。这两种异构体的差异在于，在hmGluR7编码区C末端附近有一个92个核苷酸的移码插入。hmGluR7a长度为915个氨基酸，是最近克隆的大鼠mGluR7的人类同源物。hmGluR7b长7个氨基酸，具有一个长度为23个氨基酸的新C末端。RT-PCR分析表明，mGluR7b转录本存在于野生型小鼠脑中，而在mGluR7基因敲除小鼠中不存在。Northern印迹分析表明，mGluR7的表达受发育调控。它在人胎儿脑中高水平表达，在成人大脑的许多区域中低水平表达。在稳定转染的中国仓鼠卵巢（CHO）细胞中，用L-2-氨基-4-膦酰丁酸（L-AP4）、L-丝氨酸-O-磷酸（L-SOP）或L-谷氨酸刺激hmGluR7b可抑制福斯可林诱导的cAMP积累，而（1S,3R）-1-氨基环戊烷-1,3-二羧酸（（1S,3R）-ACPD）和quisqualate（均为1mM）则无显著影响。如对大鼠mGluR7的描述，激动剂效力的顺序为：L-SOP、L-AP4>L-谷氨酸>（1S,3R）-ACPD、quisqualate。
