The G-protein-biased agents PZM21 and TRV130 are partial agonists of μ-opioid receptor-mediated signalling to ion channels.

ABSTRACT:

Background and purpose

Opioids remain the most efficient medications against severe pain; they act on receptors that couple to heterotrimeric G-proteins in the G_αi/o family. Opioids exert many of their acute effects through modulating ion channels via G_βγ subunits. Many of their side effects are attributed to β-arrestin recruitment. Several biased agonists that do not recruit β-arrestins, but activate G-protein-dependent pathways, have recently been developed. While these compounds have been proposed to be full agonists of G-protein signalling in several high throughput pharmacological assays, their effects were not studied on ion channel targets.

Experimental approach

Here, we used patch-clamp electrophysiology and Ca²⁺ imaging to test the e

SUBMITTER: Yudin Y 

PROVIDER: S-EPMC6692666 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature