Our lab has published new findings on the in vitro effects of ligand bias on primate mu opioid receptor downstream signaling in International Journal of Molecular Sciences.
Research Focus: This study investigates biased agonism at the mu opioid receptor (MOR) in rhesus macaques, focusing on agonists that have previously been reported to show different patterns of biased agonism in rodents and humans. The research addresses the critical need for translational models to evaluate the behavioral effects of candidate medications for pain treatment with reduced side effects.
Key Findings:
- Species Comparison: High degree of concordance between rhesus macaque and human MOR receptor signaling bias for all agonists tested
- Pathway Analysis: Identified downstream signaling pathways (cAMP, NF-ĸB, MAPK/JNK) that respond to MOR activation
- Ligand Evaluation: Tested six agonists including DAMGO, morphine, endomorphin-1, and TRV130
- Translational Utility: Demonstrated rhesus macaques as an effective model for future translational behavioral studies
Significance: This work addresses the opioid crisis by investigating G-protein biased MOR agonists as potential next-generation analgesics that could maintain potent analgesia while reducing side effects like respiratory depression and constipation.
Citation: Zhang X, Hutchins SD, Blough BE, Vallender EJ. In vitro effects of ligand bias on primate mu opioid receptor downstream signaling. Int J Mol Sci. 2020 Jun 3;21(11):E3999.