In vitro Pharmacology

Schematic of a metabotropic glutamate receptor depicting the location of orthosteric and allosteric sites. At right are dose-response curves from a calcium mobilization assay where mGlu7-expressing cells were treated with agonist (L-AP4) with and without pretreatment with a positive allosteric modulator (PAM, VU0422288) and a negative allosteric modulator (NAM, ADX71743.)

 

Characterization of a mGlu7 mutation, I154T, associated with neurological disease in children. Location of the I154T mutation in the crystal structure of the mGlu7 ligand binding domain. This mutation has a decreased functional response in a thallium flux assay, which can be rescued with pre-application of the PAM, VU0422288.