Differential Activation of TRPM8 by the Stereoisomers of Menthol.

ABSTRACT: The stereoisomers of menthol elicit cooling sensation to various levels. Though the high-resolution three-dimensional structures of the menthol receptor, the transient receptor potential melastatin 8 (TRPM8) ion channels, have been revolved in different states, the menthol-bound state structure is not determined and how the stereoisomers of menthol interact with TRPM8 remains largely elusive. Taking advantage of the identical atom composition but distinct spatial orientation of chemical groups in menthol stereoisomers, we performed thermodynamic mutant cycle analysis (TMCA) with patch-clamp recordings to probe the interaction between these ligands and TRPM8. By comparing (-)-menthol with (+)-neoisomenthol or (+)-neomenthol, we observed that the isopropyl or hydroxyl group in menthol intera

SUBMITTER: Chen X 

PROVIDER: S-EPMC9253294 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature