Reply to “Letter to the editor: ‘Is menthol- or icilin-induced vasodilation mediated by the activation of TRPM8?'”

Abstract

LETTERS TO THE EDITORReply to “Letter to the editor: ‘Is menthol- or icilin-induced vasodilation mediated by the activation of TRPM8?'”Christopher Johnson and Alexander ZholosChristopher Johnson and Alexander ZholosPublished Online:01 Aug 2009https://doi.org/10.1152/ajpheart.00506.2009MoreSectionsPDF (30 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat reply: The letter from Dr. Ma (3) highlights the problems that are inevitable in filling in the gaps of our knowledge of the properties of heterologously expressed transient receptor potential (TRP) channels, their expression profiles, and the functional roles in tissues and whole organisms. Not only are multiple TRP isoforms commonly expressed in native cells, but also they often do not fulfill our expectations from studies of exogenously expressed channels in cultured cells (7).Although TRPA1 has only a very limited sequence homology with TRP melastatin 8 (TRPM8), both channels can be activated by icilin and menthol. It is thus difficult for pharmacological approaches to be conclusive. However, we feel strongly that our combination of methods and the absence of evidence that TRPA1 channels are expressed on vascular myocytes (2) justify our conclusions that TRPM8 channels may, indeed, contribute to vascular tone in the vessels examined in our study with the use of menthol and icilin. The experimental approaches suggested by Ma (3) are all extremely valid. However, nonpharmacological approaches also have their own inherent problems. There are several notable examples within the field of TRP channel study where molecular interventions, such as the deletion of the gene for specific channels, have not had the effects predicted (6, 7). These studies should be done but may not be conclusive in isolation. Thus future and imminent work in the field of vascular TRPM8 and TRPA1 channels should use a combination of all the approaches available, including molecular approaches outlined by Ma (3), but should also have a strong element of functional physiology/pharmacology, using the best ligands available at the time, which are constantly being reviewed (1, 4). Indeed, controversy surrounding the roles of TRPM8 and TRPA1 proteins in cold sensation, and especially conflicting reports on the role of TRPA1 in sensory neurons (5), raises awareness that the answer to the above questions may not be simple.REFERENCES1 Bödding M, Wissenbach U, Flockerzi V. Characterisation of TRPM8 as a pharmacophore receptor. Cell Calcium 42: 618–628, 2007.Crossref | PubMed | ISI | Google Scholar2 Earley S, Gonzales AL, Crnich R. Endothelium-dependent cerebral artery dilation mediated by TRPA1 and Ca2+-activated K+ Channels. Circ Res 104: 987–994, 2009.Crossref | PubMed | ISI | Google Scholar3 Ma S. Letter to the editor: “Is menthol- or icilin-induced vasodilation mediated by the activation of TRPM8?” Am J Physiol Heart Circ Physiol. doi:10.1152/ajpheart.00460.2009.Link | ISI | Google Scholar4 Ma S, G G, Ak VE, Jf D, H H. Menthol derivative WS-12 selectively activates transient receptor potential melastatin-8 (TRPM8) ion channels. Pak J Pharm Sci 21: 370–378, 2008.PubMed | ISI | Google Scholar5 McKemy DD. How cold is it? TRPM8 and TRPA1 in the molecular logic of cold sensation. Mol Pain 1: 16, 2005.Crossref | PubMed | ISI | Google Scholar6 Nilius B, Owsianik G, Voets T, Peters JA. Transient receptor potential cation channels in disease. Physiol Rev 87: 165–217, 2007.Link | ISI | Google Scholar7 Venkatachalam K, Montell C. TRP Channels. Annu Rev Biochem 76: 387–417, 2007.Crossref | PubMed | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: C. Johnson, Centre for Vision and Vascular Science, School of Medicine, Medical Biology Ctr., Queen's Univ. Belfast, 97 Lisburn Rd., Belfast BT9 7BL, UK (e-mail: [email protected]) Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation More from this issue > Volume 297Issue 2August 2009Pages H888-H888 Copyright & PermissionsCopyright © 2009 the American Physiological Societyhttps://doi.org/10.1152/ajpheart.00506.2009History Published online 1 August 2009 Published in print 1 August 2009 Metrics