Open AccessEvaluation of G protein bias and β-arrestin 2 signaling in opioid-induced respiratory depression
Author(s) -
Jordan T Bateman,
Erica S. Levitt
Publication year - 2021
Publication title -
american journal of physiology. cell physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.432
H-Index - 181
eISSN - 1522-1563
pISSN - 0363-6143
DOI - 10.1152/ajpcell.00259.2021
Subject(s) - respiratory system , arrestin , depression (economics) , opioid , g protein , brainstem , pharmacology , medicine , neuroscience , psychology , receptor , g protein coupled receptor , economics , macroeconomics
Respiratory depression is a potentially fatal side effect of opioid analgesics and a major limitation to their use. G protein-biased opioid agonists have been proposed as "safer" analgesics with less respiratory depression. These agonists are biased to activate G proteins rather than β-arrestin signaling. Respiratory depression has been shown to correlate with both G protein bias and intrinsic efficacy, and recent work has refuted the role of β-arrestin signaling in opioid-induced respiratory depression. In addition, there is substantial evidence that G proteins do, in fact, mediate respiratory depression by actions in respiratory-controlling brainstem neurons. Based on these studies, we provide the perspective that protection from respiratory depression displayed by newly developed G protein-biased agonists is due to factors other than G protein versus arrestin bias.