TRPV1 Channel as New Target for Marine Toxins: Example of Gigantoxin I, a Sea Anemone Toxin Acting Via Modulation of the PLA2 Pathway.

Gigantoxin I, isolated from sea anemone Stichodactyla gigantea, was previously described as the first epidermal growth factor (EGF)-like toxin from natural origin. In this study, we discovered the interaction between the transient receptor potential vanilloid subtype I (TRPV1) channels and gigantoxin I. The TRPV1 channel is a non-selective cation channel involved in pain sensation and is described as pharmacological target of cnidaria venom. Our results highlight the involvement of the epidermal growth factor receptor/phospholipaseA2/arachidonic acid/lipoxygenase (EGFR/PLA2/AA/ LOX) pathway in the indirect activation of TRPV1 channels by gigantoxin I. This is the first time that this pathway is described in the indirect activation of TRPV1 channels by toxins. This knowledge not only gives insights into the possible induced effects by this new group of toxins, but also leads to a better understanding of the regulatory mechanism of TRPV1 channels themselves.