Activation of TRPA1 channel by caffeine

Abstract

Caffeine is known to have various pharmacological effects such as activation of ryanodine receptor, block of adenosine receptor and inhibition of phosphodiesterase. Masuho et al. (2005) reported that [Ca²⁺]_i increase was observed upon application of caffeine in STC1 enteric neuroendocrine cell and that it was inhibited by phospholipase C (PLC) inhibitor. The results cannot be explained by the known effects and imply the presence of a caffeine sensitive molecule whose activity or effect is dependent on PLC. We observed by [Ca²⁺]_i imaging that the [Ca²⁺]_i increase by caffeine in STC1 cells disappeared in the absence of Ca²⁺_o, showing that a caffeine sensitive Ca²⁺ permeable channel with PLC dependency is involved. We also observed the response was inhibited by blockers of Ca²⁺ permeable Transient Receptor Potential (TRP) channel, Gd³⁺ and ruthenium red. As TRPA1 channel is known to require basal PLC activity to maintain its function, we speculated TRPA1 channel is the molecule which provides caffeine sensitivity to STC1 cells. cDNA encoding TRPA1 was successfully isolated from STC1 cells by PCR. In HEK293 cells transfected with TRPA1 channel, [Ca²⁺]_i increase upon application of caffeine and its suppression by Gd³⁺ or ruthenium red were confirmed. TRPA1 channel current evoked by caffeine was also observed electrophysiologically in Xenopus oocytes. In summary, we showed for the first time that caffeine has a new pharmacological effect to increase [Ca²⁺]_i by activating TRPA1 channel on the cell surface membrane. [J Physiol Sci. 2008;58 Suppl:S78]