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Papers of the Week

Papers: 13 Jul 2019 - 19 Jul 2019

Animal Studies, Pharmacology/Drug Development

2019 Oct

J Pharmacol Exp Ther



Opioid-induced signaling and antinociception are modulated by the recently deorphanized receptor, GPR171.


McDermott MV, Afrose L, Gomes I, Devi LA, Bobeck EN
J Pharmacol Exp Ther. 2019 Oct; 371(1):56-62.
PMID: 31308196.


ProSAAS is one of the most widely expressed proteins throughout the brain and has recently been found to be upregulated in chronic fibromyalgia patients. BigLEN is a neuropeptide that is derived from ProSAAS and was recently discovered to be the endogenous ligand for the orphan G protein-coupled receptor, GPR171. While BigLEN- GPR171 has been found to play a role in feeding and anxiety behaviors, it has not yet been explored in pain and opioid modulation. The purpose of this study was to evaluate this novel neuropeptide-receptor system in opioid-induced antinociception. We found that GPR171 is expressed in GABAergic neurons within the periaqueductal gray (PAG), which is a key brain area involved in pain modulation and opioid functions. We also found that although the GPR171 agonist and antagonist do not have nociceptive effects on their own, they oppositely regulate morphine-induced antinociception with the agonist enhancing and antagonist reducing antinociception. Lastly, we showed that the GPR171 antagonist or receptor knockdown decreases signaling by the mu-opioid receptor, but not the delta-opioid receptor. Taken together, these results suggest that antagonism of the GPR171 receptor reduces MOPr signaling and morphine induced-antinociception, whereas the GPR171 agonist enhances morphine antinociception suggesting that GPR171 may be a novel target towards the development of pain therapeutics. SIGNIFICANCE STATEMENT: GPR171 is a recently deorphanized receptor that is expressed within the periaqueductal gray and can regulate mu opioid receptor signaling and antinociception. This research may contribute to the development of new therapeutics to treat pain.