The δ-opioid receptor positive allosteric modulator BMS 986187 is a G-protein-biased allosteric agonist.

ABSTRACT:

Background and purpose

The δ-opioid receptor is an emerging target for the management of chronic pain and depression. Biased signalling, the preferential activation of one signalling pathway over another downstream of δ-receptors, may generate better therapeutic profiles. BMS 986187 is a positive allosteric modulator of δ-receptors. Here, we ask if BMS 986187 can directly activate the receptor from an allosteric site, without an orthosteric ligand, and if a signalling bias is generated.

Experimental approach

We used several clonal cell lines expressing δ-receptors, to assess effects of BMS 986187 on events downstream of δ-receptors by measuring G-protein activation, β-arrestin 2 recruitment, receptor phosphorylation, loss of surface receptor expression, ERK1/ERK2 phosphoryla

SUBMITTER: Stanczyk MA 

PROVIDER: S-EPMC6514288 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature