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This talk is an activity from the FEBS Junior Section, an initiative set up by students and young researchers from some of the FEBS Constituent Societies. Each month members of the FEBS Junior Section organize an online event on either a research or a career topic. This talk was coordinated by the RSBMB Junior (the junior section of the Romanian Society of Biochemistry and Molecular Biology, RSBMB).
Speaker: Prof. Dr. Alexandru Babeș, Department of Anatomy, Physiology, and Biophysics, Faculty of Biology, University of Bucharest, Romania
Topic: “Modulation of TRPM8 function by the prostacyclin receptor: involvement of Gq/11 proteins”
Time: 19 September 2024, 19:00 (CET)
For more information: See the abstract and biosketch below and visit Prof. Dr. Alexandru Babeș' institutional webpage.
Abstract
The Transient Receptor Potential Melastatin subtype 8 (TRPM8) receptor-channel is involved in innocuous cold sensing and has a potent anti-inflammatory action. Its activation by lower temperature or chemical agonists such as menthol and icilin induces analgesic effects, reversing hypersensitivity and reducing chronic pain. On the other hand, prostacyclin (PGI2) enhances pain and inflammation by activating the prostacyclin receptor (IP-R). Due to the critical roles of TRPM8 and IP-R in the regulation of inflammatory pain, and considering their overlapping expression pattern, we analyzed the functional interaction between human TRPM8 and IP-R.
We employed transient expression of human TRPM8 and IP-R in HEK293T cells and performed intracellular calcium and cAMP measurements. Additionally, we cultured neurons from the dorsal root ganglia of mice and determined the increase in intracellular calcium triggered by TRPM8 agonist, icilin, in the presence of the IP-R agonist, cicaprost, IP-R antagonist, CAY10144 and the Gq/11 inhibitor YM254890. Our results demonstrate that the activation of IP-R by selective agonists, such as cicaprost, beraprost, and iloprost, inhibits TRPM8 independently of the Gs-cAMP pathway. The potent inhibition of TRPM8 by IP-R involves Gq/11 coupling of IP-R. These effects were also observed in neurons isolated from the dorsal root ganglia (DRGs) of mice.
Our results demonstrate that an unusual signaling pathway of IP-R, namely the coupling to Gq/11 proteins, inhibits TRPM8 which may contribute to a better understanding of the role of TRPM8 and IP-R in the regulation of pain and inflammation.
Biosketch
Alexandru Babeș is a professor of neuroscience and physiology at the University of Bucharest, Faculty of Biology. His research lab is focused on studying the peripheric nervous system and sensitivity neurons involved in pain and temperature sensing. Thus far, he has published over thirty papers in prestigious peer-reviewed journals, including Nature, Nature Medicine, Nature Communications, Journal of Neuroscience, Pain, and the Journal of Physiology. Beginning in 1995, he underwent numerous research fellowships in Germany, France, UK, and Spain. He was also a beneficiary of the Alexander von Humboldt fellowship and received the “Friedrich Wilhelm Bessel” award for his research in 2019. He was also the president of the National Romanian Council for Scientific Research since 2020.
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