What question did this study set out to answer?

The aim is to explore the effects of novel ligands on GPR151 and their interaction with morphine’s analgesic effects.

May 11, 2026Open Access

Novel Ligands for the Orphan Receptor GPR151 Modulate Morphine Action

Key Points

The aim is to explore the effects of novel ligands on GPR151 and their interaction with morphine’s analgesic effects.
Evaluated GPR151 ligands using S]-GTPγS binding assays and reporter gene expression in CHO cells expressing GPR151.
Conducted activity evaluation with structural analogs to understand ligand structure-activity relationships.
Assessed the analgesic effects of ligands in a rat model, particularly their interaction with morphine.
Ligands induced GPR151 internalization and enhanced gene expression in vitro.
An agonist enhanced morphine's analgesic effect, while a partial agonist attenuated it.
Findings indicate GPR151 as a potential drug target for reducing opioid reliance.

Abstract

S]-GTPγS binding assay. Both ligands induced GPR151 internalization and increased reporter gene expression in Chinese hamster ovary cells transiently expressing human GPR151 upon ligand stimulation. Activity evaluation employing structural analogs provided insights into a series of ligand structure-activity relationships. Administration of the unique ligands had no effect on thermal hyperalgesia in rats; however, an agonist and a partial agonist enhanced and attenuated the analgesic effect of morphine, respectively, when co-administered. These findings not only reveal the physiological role of GPR151 in pain transmission but also demonstrate its potential as a novel drug target for pain control. Our findings indicate that the development of GPR151 ligands can contribute to the reduction of opioid use.

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