Molecular determinants of positive allosteric modulation of the human metabotropic glutamate receptor 2.

ABSTRACT:

Background and purpose

The activation of the metabotropic glutamate receptor 2 (mGlu2 ) reduces glutamatergic transmission in brain regions where excess excitatory signalling is implicated in disorders such as anxiety and schizophrenia. Positive allosteric modulators (PAMs) can provide a fine-tuned potentiation of these receptors' function and are being investigated as a novel therapeutic approach. An extensive set of mutant human mGlu2 receptors were used to investigate the molecular determinants that are important for positive allosteric modulation at this receptor.

Experimental approach

Site-directed mutagenesis, binding and functional assays were employed to identify amino acids important for the activity of nine PAMs. The data from the radioligand binding and mutagenesi

SUBMITTER: Farinha A 

PROVIDER: S-EPMC4403101 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature