q&more
My watch list
my.chemie.de  
Login  

News

New Molecular Probes for Opioid Receptors

Scigraphix

Using special ligands, it was possible to prove that opioid receptors are also present as pairs of two in the cell membrane.

26-Mar-2020: It could be an important step forward in the improvement of pain therapy: Thanks to newly developed molecular probes, the behavior of individual opioid receptors can now be studied in detail.

Strong painkillers are very important in the management of patients with cancer and heart attack or requiring surgery. They extert their effect by binding to so-called opioid receptors in the body.

These painkillers have excellent efficacy, but also severe side effects. On the one hand, there is the danger of dependency, on the other hand, patients may become tolerant – i.e. the effectiveness of the drugs decreases with repeated use. This means that the dose must be increased over time to achieve the same effect.

Basic research on opioid receptors

Painkillers with less drastic undesirable effects and equally good efficacy would therefore be highly desirable. Michael Decker, Professor of Pharmaceutical and Medicinal Chemistry at Julius-Maximilians-Universität (JMU) Würzburg, in Bavaria, Germany, is pursuing research in this field. Among other things, his team wants to expand the basic knowledge about opioid receptors.

Decker now presents new findings in this field in the journal "Angewandte Chemie" together with Sébastien Granier from the Institut de Génomique Fonctionelle in Montpellier, Peter Gmeiner from the University of Erlangen-Nuremberg, and as main collaborator Professor Davide Calebiro from the University of Birmingham, UK. The JMU PhD students Christian Gentzsch, Kerstin Seier, and Antonios Drakopoulos were also involved in the work.

The receptors form short-lived pairs

The team dealt with a question that has been highly debated in the field so far. "It is still unclear whether the analgesic effect of opioids is mediated by individual receptors or whether it is necessary for the receptors to aggregate into pairs or larger molecular complexes," said Decker. Evidence has already been found for all these possibilities.

"Our results help reconciling some of the previously contradictory observations," says Davide Calebiro, who until recently was a researcher at JMU. "We found that most opioid receptors exist as individual entities in the cell membrane. However, a small proportion forms pairs of two. Although the lifespan of these pairs is short, they might contribute to the function of this important family of receptors."

Journal classifies work as "Highly Important“

This finding might be very important: "There is evidence that the receptor pairs have different pharmacological effects than individual receptors," said Decker. Therefore, it might be possible to develop new painkillers with a more favourable effect profile on the basis of this knowledge.

Due to the importance of these new findings, "Angewandte Chemie" has classified the publication of the JMU researchers as "highly important". It is freely available on the Web. In addition, the work was selected for one of the journal covers.

Highly selective ligands developed

The research team came to its conclusion because it had previously developed highly selective fluorescent ligands for a subtype of the receptors, the so-called mu opioid receptor (MOR). This is the most important of the three receptor subtypes and is responsible for the desired pain-relieving but also for the addictive effect. The new ligands can be used as molecular probes to label the receptor highly specifically and to observe its behaviour in living cells using single-molecule fluorescence microscopy.

The researchers are now working on the production of fluorescent ligands for the other two receptor subtypes (delta and kappa; DOR and KOR) in order to analyse their behaviour in the cell membrane as well. This has already been achieved with KOR (A. Drakopoulos et al., Journal of Medicinal Chemistry 2020, in print).

Original publication:
"Selective and Wash-Resistant Fluorescent Dihydrocodeinone-Derivatives Allow Single-Molecule Imaging of mu-Opioid Receptor Dimerisation", Angewandte Chemie; 2020

Facts, background information, dossiers

  • opioid receptors
  • pain therapies
  • painkillers

More about Uni Würzburg

  • News

    Tracking Down False Parkers in Cancer Cells

    In squamous cell carcinoma, a protein ensures that unneeded proteins are no longer disposed of. A research team at the University of Würzburg has switched off this protein for the first time. Squamous cell carcinoma is a very unusual type of cancer. They occur in many tissues – for example ... more

    Virus multiplication in 3D

    Vaccinia viruses serve as a vaccine against human smallpox and as the basis of new cancer therapies. Two studies now provide fascinating insights into their unusual propagation strategy at the atomic level. For viruses to multiply, they usually need the support of the cells they infect. In ... more

    Achilles Heel of Tumour Cells

    In almost all cases of colon cancer, a specific gene is mutated – this offers opportunities to develop broadly effective therapeutic approaches. Research teams in Würzburg have taken this a step further. In 90 percent of all cases of colon cancer, the tumour cells have one thing in common: ... more

  • q&more articles

    High-tech in the beehive

    Healthy honeybee colonies are crucial to maintaining the natural diversity of flowering plants and the global production of plant-derived foodstuffs. As much as 35 % of this production depends on insect-based pollination, in which the honeybee (Apis mellifera) plays a leading role. For fund ... more

  • Authors

    Prof. Dr. Jürgen Tautz

    studied biology, geography and physics at the University of Konstanz before receiving his doctorate from the University on an ecology-related subject. Work in insect, fish and frog bio-acoustics was followed by his foundation of the BEEgroup at the University of Würzburg in 1994, a group th ... more

  • Videos

    High-tech in the beehive

    more

q&more – the networking platform for quality excellence in lab and process

The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.

> more about q&more

q&more is supported by:

 

Your browser is not current. Microsoft Internet Explorer 6.0 does not support some functions on Chemie.DE