Medications that target opioid receptors can cause serious adverse effects. Every day, thousands of people around the world die as a result of overdoses of opioids, including fentanyl.
A team of worldwide experts investigated the molecular mechanisms of these active compounds. The study, conducted by biophysicist Dr. Matthias Elgety of the University of Leipzig in partnership with research groups in the United States and China, has recently been published in the journal Nature.
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Opioid receptors are of major medical interest because opioids influence pain perception. “Our findings highlight how an opioid receptor can serve multiple functions. It could relieve pain while controlling digestion or breathing,” says Dr. Elgety, co-first author of the paper.
In the current study, biophysicists collaborated with international scientists, including the research group of Nobel laureate Brian Kobilka of Stanford University. They found that superagonists, such as fentanyl, stabilize a state of the receptor that causes particularly effective and long-lasting signal transmission. This means that superagonists are especially powerful and therefore dangerous. In the current study, the researchers used electron spin resonance and single-molecule fluorescence spectroscopy to determine the structural effects of different states of the opioid receptor and different binding partners.
Opioid receptors are members of the large family of G protein-coupled receptors (GPCRs), which regulate many signaling processes in the body such as taste and smell, while binding other neurotransmitters and hormones or being activated by light. Understanding the molecular interactions of these receptors with drugs and other signaling proteins is of great importance for drug development. Since 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 opioid receptors. They are normally found in the body’s cells, interacting with many other proteins and molecules,” says Dr. Elgeti. “Further research into molecular interactions is needed.” The new study is an important building block in basic research, with further studies needed to ultimately develop better and safer drugs.
