Flor P J, Lukic S, Rüegg D, Leonhardt T, Knöpfel T, Kuhn R
Molecular and Cellular Biology, CNS Research, Basle, Switzerland.
Neuropharmacology. 1995 Feb;34(2):149-55. doi: 10.1016/0028-3908(94)00149-m.
A cDNA encoding the human metabotropic glutamate receptor type 4 (hmGluR4) was isolated from human brain cDNA libraries by cross-hybridization with rat mGluR4 probes. The deduced amino acid sequence of human mGluR4 consists of 912 residues and shows a sequence identity of 96% to the amino acid sequence of rat mGluR4. Northern blot analyses indicate that hmGluR4 is strongly expressed in the cerebellum of the adult human brain but also at low levels in hippocampus, hypothalamus and thalamus. Stimulation of hmGluR4 with L-2-amino-4-phosphonobutyrate (L-AP4), L-serine-O-phosphate (L-SOP), L-glutamate or (1S,3R)-1-aminocyclo-pentane-1,3-dicarboxylic acid ((1S,3R)-ACPD) in stably transfected Chinese hamster ovary (CHO) cells depressed forskolin-induced cAMP accumulation, whereas quisqualate (0.5 mM) was ineffective. The rank order of agonist potencies is: L-AP4 > L-SOP > L-glutamate > (1S,3R)-ACPD >> quisqualate. (R,S)-alpha-methyl-4-carboxyphenylglycine (1 mM), a reported antagonist at some mGluR subtypes, did not reduce the depression of forskolin-induced cAMP accumulation by L-AP4.
通过与大鼠mGluR4探针进行交叉杂交，从人脑cDNA文库中分离出了编码人代谢型谷氨酸受体4（hmGluR4）的cDNA。推导的人mGluR4氨基酸序列由912个残基组成，与大鼠mGluR4的氨基酸序列具有96%的序列同一性。Northern印迹分析表明，hmGluR4在成人大脑的小脑中强烈表达，但在海马体、下丘脑和丘脑也有低水平表达。在稳定转染的中国仓鼠卵巢（CHO）细胞中，用L-2-氨基-4-膦酸丁酸（L-AP4）、L-丝氨酸-O-磷酸（L-SOP）、L-谷氨酸或（1S,3R）-1-氨基环戊烷-1,3-二羧酸（（1S,3R）-ACPD）刺激hmGluR4可抑制福斯高林诱导的cAMP积累，而喹啉酸（0.5 mM）则无效。激动剂效力的顺序为：L-AP4 > L-SOP > L-谷氨酸 > （1S,3R）-ACPD >> 喹啉酸。（R,S）-α-甲基-4-羧基苯基甘氨酸（1 mM），一种报道的某些mGluR亚型拮抗剂，并未降低L-AP4对福斯高林诱导的cAMP积累的抑制作用。
