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Leipzig: Drugs that target opioid receptors can have serious adverse effects. Every day, thousands of people worldwide die as a result of opioid overdoses, including fentanyl.
A worldwide team of experts investigated the molecular mechanisms of these active compounds. The study, conducted by Dr Matthias Elgeti, a biophysicist at Leipzig University, in partnership with research groups from the United States and China, has recently been published in the journal Nature.
Opioid receptors are of major medical interest because opioids influence pain perception. “Our findings shed light on how an opioid receptor might fulfil several tasks. Dr Elgeti, co-first author of the paper, notes that it can relieve pain while also regulating digestion or breathing.
In the current study, the biophysicist collaborated with international scientists, including the research group of Nobel laureate Brian Kobilka from Stanford University. They discovered that superagonists, such as fentanyl, stabilise a state of the receptor that causes particularly effective and long-lasting signal transmission. This means that superagonists are particularly potent and therefore dangerous. In the current study, the researchers used electron spin resonance and single-molecule fluorescence spectroscopy to determine different states of the opioid receptor and the structural effects of different binding partners.Opioid receptors are members of the large family of G protein-coupled receptors (GPCRs), which control many signalling processes in the body, such as taste and smell, while others bind neurotransmitters and hormones or are activated by light. Understanding the molecular interactions of these receptors with drugs and other signalling proteins is very important for drug development. As all GPCRs are structurally very similar, the researchers hope that their findings on the opioid receptor can be applied to other receptors.
“This study involved isolating the opioid receptors. They are normally found in the body’s cells, interacting with many other proteins and molecules. Further research into the molecular interactions is therefore needed to gain a full understanding of the regulatory mechanisms,” says Dr Elgeti. The new study is an important building block in basic research, with further studies needed to ultimately develop better and safer medicines.
