Volatile anaesthetics inhibit the thermosensitive nociceptor ion channel transient receptor potential melastatin 3 (TRPM3)
| Autor: | Attila Gábor Szöllősi, Balázs Kelemen, Balázs István Tóth, Attila Oláh, Tamás Bíró, János Almássy, János Posta, Thomas Voets, Erika Lisztes, Martin Hanyicska, Anita Vladár, Zsófia Pénzes |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Nociception
0301 basic medicine TRPV1 TRPM Cation Channels Thermosensation Pharmacology Biochemistry TRP ion channels Mice 03 medical and health sciences Transient receptor potential channel chemistry.chemical_compound 0302 clinical medicine Ganglia Spinal TRPM8 medicine Animals Humans TRPM3 Ion channel Dose-Response Relationship Drug 3. Good health Mice Inbred C57BL HEK293 Cells 030104 developmental biology chemistry Volatile anaesthetics 030220 oncology & carcinogenesis Anesthetics Inhalation Nociceptor Halothane Pregnenolone sulfate medicine.drug |
| Zdroj: | Biochemical Pharmacology |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/j.bcp.2020.113826 |
| Popis: | BACKGROUND: Volatile anaesthetics (VAs) are the most widely used compounds to induce reversible loss of consciousness and maintain general anaesthesia during surgical interventions. Although the mechanism of their action is not yet fully understood, it is generally believed, that VAs depress central nervous system functions mainly through modulation of ion channels in the neuronal membrane, including 2-pore-domain K+ channels, GABA and NMDA receptors. Recent research also reported their action on nociceptive and thermosensitive TRP channels expressed in the peripheral nervous system, including TRPV1, TRPA1, and TRPM8. Here, we investigated the effect of VAs on TRPM3, a less characterized member of the thermosensitive TRP channels playing a central role in noxious heat sensation. METHODS: We investigated the effect of VAs on the activity of recombinant and native TRPM3, by monitoring changes in the intracellular Ca2+ concentration and measuring TRPM3-mediated transmembrane currents. RESULTS: All the investigated VAs (chloroform, halothane, isoflurane, sevoflurane) inhibited both the agonist-induced (pregnenolone sulfate, CIM0216) and heat-activated Ca2+ signals and transmembrane currents in a concentration dependent way in HEK293T cells overexpressing recombinant TRPM3. Among the tested VAs, halothane was the most potent blocker (IC50 = 0.52 ± 0.05 mM). We also investigated the effect of VAs on native TRPM3 channels expressed in sensory neurons of the dorsal root ganglia. While VAs activated certain sensory neurons independently of TRPM3, they strongly and reversibly inhibited the agonist-induced TRPM3 activity. CONCLUSIONS: These data provide a better insight into the molecular mechanism beyond the analgesic effect of VAs and propose novel strategies to attenuate TRPM3 dependent nociception. ispartof: BIOCHEMICAL PHARMACOLOGY vol:174 ispartof: location:England status: published |
| Databáze: | OpenAIRE |
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