Researchers from the University of Geneva (UNIGE) have discovered new insights into how natural and therapeutic opioids work in the human body, according to a study published in the journal Science Advances. Opioid drugs, including morphine and fentanyl, are widely used to alleviate severe pain but are associated with a high risk of addiction. Natural opioids, such as endorphins, are produced by the human body and can block pain perception and increase well-being.
The study found that therapeutic opioids penetrate inside the cells to activate opioid receptors, while natural opioids cannot enter cells and activate only receptors located on the cell surface. The activated receptors’ location could explain why opioid drugs trigger different physiological responses from those induced by natural opioids.
The team used biosensors to detail what happens at different locations within the cell, allowing them to detect whether specific receptors were activated and able to initiate a response. Ultimately, the scientists discovered that the site of GPCR activation modifies the response triggered by opioids and the signals involved in pain relief.
The researchers also observed that the types of lipids surrounding the GPCR influence the responses they transmit, which may explain the variations in the effects of opioid drugs. They hope to discover if changes in membrane lipids occurring in metabolic diseases, such as diabetes, can influence the efficacy and unwanted effects of GPCR drugs.
To confirm this hypothesis, they are planning in vivo experiments intending to design better-targeted therapeutics with improved efficacy and reduced side effects.
The study provides insight into the mechanisms responsible for different reactions to opioid drugs and could help develop safer, more effective medications that better mimic natural opioids. These findings also highlight the membrane lipid’s crucial role in the effects of opioid drugs.