Medical Research

Fine Regulation of Receptors Achieved

New agents set off only one signal instead of several

7. 11. 2012 | A large number of drugs for cardiac insufficiency, high blood pressure and other conditions regulate the function of receptors. Researchers from Würzburg, Bonn and Milan have designed new agents for novel fine adjustments of these receptors.
Beta blockers are drugs for high blood pressure. In the organism, they attach themselves to specific receptors that would otherwise bind to the "stress hormone" adrenaline. The blockage of the receptor molecules renders the adrenaline ineffective - the blood pressure drops. All body cells have a great variety of similar receptors on their surface. Their function is to receive messages from the environment and to adjust the cell function accordingly. The G protein coupled receptors (GPCR) comprise a large group of receptors. They serve for processing external or internal stimuli, such as odors and flavors, or nerve and hormone signals.

Prof. Ulrike Holzgrabe in her office
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Prof. Ulrike Holzgrabe in her office
"A lot of our drugs modify the function of specific GPC receptors," Ulrike Holzgrabe explains, professor of pharmaceutics at the University of Würzburg. The receptors are activated or deactivated in this process. In case of GPC receptors, however, the "activation" often involves setting off several signals with various meanings within the cell. This can lead to undesirable side effects.
A research team from Würzburg, Bonn and Milan has now discovered a completely novel approach: They identified an area in the protein structure of a GPCR that can be used as a "switch point" for signals.

What the scientists achieved: With specially designed agents, they were able to activate a certain GPCR, the so-called muscarinic receptor, at a particular point while giving the response signal a specific direction at another point. In this way, the activation does not set off several signals, but only one – the desired one in each case. "Numerous members of the GPCR family have such switch points in their protein structure, so that further receptors might be regulated in this novel way," says Holzgrabe. This opens the prospect of developing innovative drugs which manipulate the cell function in a more targeted way, enabling a more effective and well tolerated treatment. Next, the researchers are going to design further agents in order to get more insights into the signal transduction of GPC receptors.   (© University of Würzburg / AcademiaNet)
Robert Emmerich

More information


  • "The allosteric vestibule of a seven transmembrane helical receptor controls G-protein coupling", Andreas Bock, Nicole Merten, Ramona Schrage, Clelia Dallanoce, Julia Bätz, Jessica Klöckner, Jens Schmitz, Carlo Matera, Katharina Simon, Anna Kebig, Lucas Peters, Anke Müller, Jasmin Schrobang-Ley, Christian Tränkle, Carsten Hoffmann, Marco De Amici, Ulrike Holzgrabe, Evi Kostenis & Klaus Mohr, Nature Communications 3, 4. September 2012, DOI 10.1038/ncomms2028


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