Capsaicin indirectly regulates TRPA1 via the arachidonic acid cascade, resulting in TJ opening.

Autor: Yusuke Kanda, Minagi Mukaiyama, Yohei Yamasaki, Takeo Usui, Yoko Nagumo
Předmět:
Zdroj: Bioscience, Biotechnology & Biochemistry; Jan2024, Vol. 88 Issue 1, p44-52, 9p
Abstrakt: Capsaicin induces the reversible opening of tight junctions (TJs) and enhances the delivery of hydrophilic macromolecules through a paracellular route. We previously revealed that TRPA1 is involved in the capsaicin-induced Ca2+ influx and TJ permeability increase, although there are no reports that capsaicin directly activates TRPA1. In this study, we investigated the upstream factors of TRPA1 using RNA-seq analysis, and found that the cyclooxygenase 2 (COX2) gene was upregulated by capsaicin. Cyclooxygenase 2 converts arachidonic acid (AA), a metabolite by phospholipase A2 (PLA2), to prostaglandins. Prostaglandin E2 (PGE2) production was stimulated by capsaicin, and capsaicin-induced Ca2+ influx was effectively inhibited by PLA2 and COX2 inhibitors. The AA-induced TJ permeability increase was inhibited by a TRPA1 antagonist, but the capsaicin- and AA-induced TJ permeability increases were hardly inhibited by a COX2 inhibitor. These results suggest that capsaicin-induced PLA2 activation and AA production are the important steps for the TJ permeability increase. [ABSTRACT FROM AUTHOR]
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