Nociceptive TRP channels are molecular targets of a bird repellent pulegone

Abstract

Pulegone is one of repellents for prevention from economic loss caused by birds. Chemical repellents often elicit unpleasant sensations and sensory irritation. It is recognized that some TRP channels expressing sensory neuros are related to nociception. Here we determined the molecular mechanisms of the repellent action of pulegone. In isolated chicken sensory neurons, pulegone increased the intracellular Ca²⁺ concentration ([Ca²⁺]_i). There were two types of neurons regarding the responsiveness to pulegone. One was responded to pulegone at low concentrations and the other at high concentrations. Pharmacological analyses revealed that the former was exclusively mediated by TRP melastatin 8 (TRPM8), and the latter by both TRP ankyrin 1 (TRPA1) and TRPM8. Heterologously expressed chicken TRPM8 and TRPA1 were also stimulated by pulegone. At high concentrations, pulegone inhibited chicken TRPM8 but not chicken TRPA1. Mouse orthologues were also activated by pulegone. Unlike chicken TRPA1, its high concentration inhibited mouse TRPA1. In chicks, intraplantar application of pulegone evoked pain-related behaviors which were inhibited by systemic administration of an antagonist for TRPA1, but not for TRPM8. These results indicate that pulegone activates both TRPM8 and TRPA1 in chicken sensory neurons and at high concentrations it suppresses the former but not the latter. Furthermore, there are species differences in the sensitivity to pulegone between bird and mammal. These data suggest that the molecular target for pulegone in avian species may be mainly nociceptive TRPA1 channels.