studies with mice, guinea pig, and human tissues and in guinea pigs indicate that another arachidonic acid metabolite, prostaglandin e2, operates through its prostaglandin ep3 g protein coupled receptor to trigger cough responses. its mechanism of action does not appear to involve direct binding to trpa1 but rather the indirect activation and/or sensitization of trpa1 as well as trpv1 receptors. genetic polymorphism in the ep3 receptor (rs11209716), has been associated with ace inhibitor-induce cough in humans.