Recently, scientists from the Immunopharmacology and Interactomics group of the Infection and Immunity Department of the Luxembourg Institute of Health (LIH) in collaboration with the RTI International Center for Drug Discovery (RTI), a non-profit research institute, have shown that ‘conolidin’, a natural pain reliever is extracted from the pinwheel flower that is traditionally used in Chinese medicine. It additionally, interacts with the recently identified opioid receptor ACKR3 / CXCR7, which regulates naturally, produced opioid peptides in the brain. The researchers also developed a synthetic analogue of conolidin, RTI-5152-12, that shows even greater activity at the receptor. These results were published on June 3rd, 20201 in the international journal called Signal Transduction and Targeted Therapy (Nature editorial group). It further expands the understanding of pain regulation and opens up alternative therapeutic avenues for the treatment of chronic pain.
Opioid peptides are small proteins that mediate relief from pain and emotions, including euphoria, anxiety, stress, and depression, by interacting with classic receptors known as "molecular switches" in the brain. Dr. Andy Chevigné, director of Immunopharmacology and Interactomics, and his team had previously identified the chemokine receptor ACKR3 as a novel atypical fifth opioid receptor with high affinity for several natural opioids (Nature Communications, Meyrath et al., 2020). AACKR3 acts as a "scavenger" that "catches" secreted opioids and prevents them from binding to classical receptors, which dampens their analgesic activity and acts as a regulator of the opioid system. In the current study, researchers identified ACKR3 as the most sensitive target for conolidin, an alkaloid with analgesic properties, by screening 240 receptors for their ability to be activated or inhibited by this molecule. They confirmed that conolidin binds to the recently identified opioid receptor ACKR3 without any affinity for the others by blocking ACKR3 and preventing it from capturing naturally secreted opioids. It increases its availability for interaction with classic receptors. This is the basis for the beneficial effects of this medicine traditionally used for pain relief.
