Abstract

Mustard and horseradish get their zing from isothiocyanates, which depolarize nociceptors (sensory neurons that detect pain). Jordt et al. used calcium imaging to investigate the mechanism by which allyl isothiocyanate (mustard oil) acts and found that it elicited an increase in intracellular calcium in about 35% of dissociated rat trigeminal sensory neurons. Neurons stimulated by Δ 9 -tetrahydrocannabinol (THC, the psychoactive ingredient in marijuana) were also sensitive to mustard oil. THC- and mustard oil-dependent increases in calcium were sensitive to ruthenium red, which blocks some transient receptor potential (TRP) family cation channels, as were currents induced by these compounds measured by whole-cell patch clamp analysis. HEK 293 cells transfected with rat or human ANKTM1 (a TRP family channel) responded to mustard oil and various other natural isothiocyanate compounds, as well as to THC, but not to capsaicin (the active ingredient in chili papers, which activates the TRPV1 cation channel), with increases in intracellular calcium. Similarly, isothiocyanates, wasabi and mustard extracts, and THC all elicited currents in Xenopus oocytes expressing ANKTM1. These data suggest that THC and mustard oil excite the same set of sensory neurons through similar mechanisms involving the TRP family channel ANKTM1 and support previous research suggesting a role for TRP channels as cannabinoid receptors. S.-E. Jordt, D. M. Bautista, H.-H. Chuang, D. D. McKemy, P. M. Zygmunt, E. D. Hogestatt, I. D. Meng, D. Julius, Nature 427 , 260-265 (2004). [Online Journal]

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