The thermo- and pain-sensitive Transient Receptor Potential Melastatin 3 and 8 (TRPM3 and TRPM8) ion channels are functionally associated in the lipid rafts of the plasma membrane. We have already described that cholesterol and sphingomyelin depletion, or inhibition of sphingolipid biosynthesis decreased the TRPM8 but not the TRPM3 channel opening on cultured sensory neurons. We aimed to test the effects of lipid raft disruptors on channel activation on TRPM3- and TRPM8-expressing HEK293T cells in vitro, as well as their potential analgesic actions in TRPM3 and TRPM8 channel activation involving acute pain models in mice. CHO cell viability was examined after lipid raft disruptor treatments and their effects on channel activation on channel expressing HEK293T cells by measurement of cytoplasmic Ca2+ concentration were monitored. The effects of treatments were investigated in Pregnenolone-Sulphate-CIM-0216-evoked and icilin-induced acute nocifensive pain models in mice. Cholesterol depletion decreased CHO cell viability. Sphingomyelinase and methyl-beta-cyclodextrin reduced the duration of icilin-evoked nocifensive behavior, while lipid raft disruptors did not inhibit the activity of recombinant TRPM3 and TRPM8. We conclude that depletion of sphingomyelin or cholesterol from rafts can modulate the function of native TRPM8 receptors. Furthermore, sphingolipid cleavage provided superiority over cholesterol depletion, and this method can open novel possibilities in the management of different pain conditions.

• MeSH
• analgetika farmakologie   terapeutické užití   MeSH
• beta-cyklodextriny * farmakologie   MeSH
• bolest chemicky indukované   farmakoterapie   metabolismus   MeSH
• CHO buňky MeSH
• cholesterol metabolismus   MeSH
• Cricetulus MeSH
• HEK293 buňky MeSH
• kationtové kanály TRPM * metabolismus   genetika   MeSH
• lidé MeSH
• membránové mikrodomény metabolismus   účinky léků   MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• pregnenolon farmakologie   MeSH
• pyrimidinony farmakologie   MeSH
• sfingomyelinfosfodiesterasa * metabolismus   farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• antiparkinsonika MeSH
• genetická terapie MeSH
• jednofotonová emisní výpočetní tomografie MeSH
• Parkinsonova nemoc MeSH
• parkinsonské poruchy genetika   MeSH
• pozitronová emisní tomografie MeSH
• syndrom neklidných nohou diagnóza   patofyziologie   terapie   MeSH
• Publikační typ
• sborníky MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• neurologie