Molecular cloning, functional expression and pharmacological characterization of the human metabotropic glutamate receptor type 4.

Abstract:

: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.

journal_name

Neuropharmacology

journal_title

Neuropharmacology

authors

Flor PJ,Lukic S,Rüegg D,Leonhardt T,Knöpfel T,Kuhn R

doi

10.1016/0028-3908(94)00149-m

subject

Has Abstract

pub_date

1995-02-01 00:00:00

pages

149-55

issue

2

eissn

0028-3908

issn

1873-7064

pii

002839089400149M

journal_volume

34

pub_type

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