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Molecular Cloning, Functional Expression and Pharmacological Characterization of the Human Metabotropic Glutamate Receptor Type 2
Author(s) -
Flor P. J.,
Lindauer K.,
Püttner I.,
Rüegg D.,
Lukic S.,
Knöpfel T.,
Kuhn R.
Publication year - 1995
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1995.tb00666.x
Subject(s) - metabotropic glutamate receptor 2 , metabotropic glutamate receptor , biology , chinese hamster ovary cell , microbiology and biotechnology , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 8 , metabotropic glutamate receptor 5 , complementary dna , biochemistry , receptor , glutamate receptor , gene
A cDNA encoding the human metabotropic glutamate receptor type 2 (hmGluR2) was isolated from human brain cDNA libraries by cross‐hybridization with rat mGluR2 probes. The deduced amino acid sequence of the human mGluR2 receptor consists of 872 residues and shows a sequence identity of 97% to the amino acid sequence of rat mGluR2. Northern blot analyses showed that hmGluR2 is widely expressed in different regions of the adult brain as well as in fetal human brain. Genomic Southern blotting localized the mGluR2 gene to human chromosome 3. Chinese hamster ovary (CHO) cells stably transfected with the cloned hmGluR2 cDNA exhibit agonist induced depression of forskolin‐stimulated cAMP accumulation. A direct comparison of CHO cells stably expressing human and rat mGluR2 with five agonists revealed the same rank order of potency [(2S,3S,4S)‐α‐(carboxycyclopropyl)‐glycine » (1 S ,3 R )‐1‐aminocyclopentane‐1,3‐dicarboxylic acid = l ‐glutamate » quisqualate = l ‐2‐amino‐4‐phosphonobutyric acid] and similar EC 50 values for both homologous receptors. ( R.S )‐a‐methyl‐4‐carboxyphenylglycine, a reported antagonist at some mGluR subtypes, reduced the depression of forskolin‐induced cAMP accumulation by (1 S ,3 R )‐ACPD in both human and rat mGluR2.