EP1 receptors are responsible for COX-2 mediated neurotoxicity

Abstract

There is increasing evidence that cyclooxygenase-2 (COX-2), a rate-limiting enzyme for prostanoid synthesis, is involved in the mechanism of ischemic brain injury. However, the reaction products responsible COX-2-mediated neurotoxicity have not been defined. Prostaglandin E2 (PGE2) is the major COX-2 derived prostanoid produced following brain injury and is involved in the mechanisms of glutamate excitotoxicity (Ann. Neurol. 55, 668). PGE2 acts on four receptor subtypes (EP1-4). While activation of EP2 receptors is neuroprotective (J. Neurosci. 24, 257), EP1 receptors mediate injury in other organs (Hypertension 42, 1183). Therefore, in this study we tested the hypothesis that EP1 receptors mediate the neurotoxicity exerted by COX-2.