AbbreviationsCFAcomplete Freund's adjuvantRGSregulator of G protein signallingFSTforced swim testNTGnitroglycerinIntroductionGPCRs are a diverse family of membrane bound receptors that regulate a wide array of biological functions. Canonically, GPCRs regulate these processes through activation of G proteins which subsequently interact with a variety of downstream effectors. Following agonist activation, a GPCR is phosphorylated by GPCR kinases and internalized following recruitment of arrestins. In recent years, it has become apparent that GPCRs can signal through G protein‐independent mechanisms (Galandrin et al., ) by directly recruiting arrestins that can also promote signalling from GPCRs (Reiter et al., ). Furthermore, ligands that act at the same orthosteric site on a receptor can stabilize distinct active conformations that preferentially signal through distinct G protein or arrestin subtypes. This phenomenon, known as functional selectivity or biased agonism, has been observed with many GPCRs including the β2 adrenoceptor (Drake et al., ), the CB1 cannabinoid receptor (Hudson et al., ), as well as μ‐, κ‐ and δ‐opioid receptors (Pradhan et al., ).The δ opioid receptor (δ‐receptor) is a class A GPCR and interacts with Gαi/o proteins. Activation of the δ‐receptor in rodents has been shown to produce antinociception, antihyperalgesia, anxiolytic effects and antidepressant‐like effects without the constipation,
British Journal of Pharmacology – Wiley
Published: Jan 1, 2018
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