title: Carvacrol is a novel inhibitor of Drosophila TRPL and mammalian TRPM7 channels.
abstract: Transient receptor potential (TRP) channels are essential components of biological sensors that detect changes in the environment in response to a myriad of stimuli. A major difficulty in the study of TRP channels is the lack of pharmacological agents that modulate most members of the TRP superfamily. Notable exceptions are the thermoTRPs, which respond to either cold or hot temperatures and are modulated by a relatively large number of chemical agents. In the present study we demonstrate by patch clamp whole cell recordings from Schneider 2 and Drosophila photoreceptor cells that carvacrol, a known activator of the thermoTRPs, TRPV3 and TRPA1 is an inhibitor of the Drosophila TRPL channels, which belongs to the TRPC subfamily. We also show that additional activators of TRPV3, thymol, eugenol, cinnamaldehyde and menthol are all inhibitors of the TRPL channel. Furthermore, carvacrol also inhibits the mammalian TRPM7 heterologously expressed in HEK cells and ectopically expressed in a primary culture of CA3-CA1 hippocampal brain neurons. This study, thus, identifies a novel inhibitor of TRPC and TRPM channels. Our finding that the activity of the non-thermoTRPs, TRPL and TRPM7 channels is modulated by the same compound as thermoTRPs, suggests that common mechanisms of channel modulation characterize TRP channels.
authors.affiliation: Department of Physiology, Kühne Minerva Center for Studies of Visual Transduction, Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Parnas
authors.forename: Maximilian
authors.initials: M
authors.lastname: Peters
authors.forename: Daniela
authors.initials: D
authors.lastname: Dadon
authors.forename: Shaya
authors.initials: S
authors.lastname: Lev
authors.forename: Irena
authors.initials: I
authors.lastname: Vertkin
authors.forename: Inna
authors.initials: I
authors.lastname: Slutsky
authors.forename: Baruch
authors.initials: B
authors.lastname: Minke
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001892:Camphanes / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D000081005:Cyclohexane Monoterpenes; D000081007:Cymenes; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors*; D004331:Drosophila melanogaster / Q000378:metabolism*; D005054:Eugenol / Q000737:chemistry / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008322:Mammals / Q000378:metabolism*; D008610:Menthol / Q000737:chemistry / Q000494:pharmacology; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors*; D013943:Thymol / Q000737:chemistry / Q000494:pharmacology; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors*
chemical_list: D001892:Camphanes; D000081005:Cyclohexane Monoterpenes; D000081007:Cymenes; D029721:Drosophila Proteins; D039821:Monoterpenes; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels; C074192:trpl protein, Drosophila; D008610:Menthol; D013943:Thymol; D005054:Eugenol; D000171:Acrolein; C075856:carveol; C073316:carvacrol; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; C022871:isoborneol; C012843:cinnamaldehyde