Morphine-induced respiratory depression is independent of β-arrestin2 signalling.

ABSTRACT:

Background and purpose

GPCRs can signal through both G proteins and β-arrestin2. For the μ-opioid receptor, early experimental evidence from a single study suggested that G protein signalling mediates analgesia, whereas β-arrestin2 signalling mediates respiratory depression and constipation. Consequently, for more than a decade, much research effort has been focused on developing biased μ-opioid agonists that preferentially target G protein signalling over β-arrestin signalling, as it was believed that such drugs would be analgesics devoid of respiratory depressant activity. However, the prototypical compounds that have been developed based on this concept have so far failed in clinical and preclinical development.

Experimental approach

The present study was set up to re-exa

SUBMITTER: Kliewer A 

PROVIDER: S-EPMC7280004 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature