Anandamide Metabolites Protect against Seizures through the TRP Channel Water Witch in Drosophila melanogaster.

ABSTRACT: Endocannabinoids protect against seizures, but their mechanism of action is still unclear, as they can have effects independent of known cannabinoid receptors. Using Drosophila melanogaster, which lacks canonical cannabinoid receptors, we report that the endocannabinoids anandamide and 2-arachidonoylglycerol protect against seizures in multiple fly seizure models. Surprisingly, inhibition of anandamide catabolism renders flies insensitive to protection by anandamide, indicating that anandamide metabolites are responsible for seizure protection. Consistent with this finding, arachidonic acid, a direct metabolite of anandamide, protects against seizures. To identify downstream effectors, we test for a role of transient receptor potential (TRP) channels and find that the TRPV1 antagonist caps

SUBMITTER: Jacobs JA 

PROVIDER: S-EPMC9161705 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature