Heterogeneous expression and regulation of hippocampal prostaglandin E2 receptors

Although prostaglandin E2 (PGE2) has been shown to be critical to hippocampal synaptic signaling and neuronal survival, it is still not clear which subtypes of PGE2 receptors (EPs) are expressed and how these EPs are regulated in the hippocampus. To address these questions, the expression of the EPs was profiled in the hippocampus. Messenger RNAs and proteins of the four receptors, EP 1-4, were detected both in the hippocampus and in the neocortex. EP 2 and EP 3 appeared in greater abundance, whereas EP 1 and EP 4 were barely detectable. EP 1, EP 2 and EP 4 were mainly colocalized with synaptophysin, suggesting the presence of EP 1, EP 2, and EP 4 in presynaptic terminals. It appeared that interleukin-1 beta increased the expression of EP 2 and EP 4 mRNAs. A blockade of synaptic transmission with either tetrodotoxin or MK-801 plus 6,7-dinitroquinoxaline-2,3-dione (DNQX) for 6 hr increased EP 3 and EP 4 mRNA, whereas high K(+) (90 mM) or 4-aminopyridine enhanced EP 2 and EP 4. The EP 1 level did not change significantly under these conditions. The expressions of EP 2, EP 4, and EP 3 were further elevated or reduced in neurons treated with high K(+) for 24 hr. However, mRNA of EP 3 was down-regulated in neurons treated with tetrodotoxin or MK-801 plus DNQX for 24 hr. In addition, both EP 2 and EP 4 mRNAs were up-regulated within 4 hr after high-frequency stimulation associated with long-term potentiation induction in hippocampal slices. Our results indicate that the four EPs are heterogeneously expressed in the hippocampus, and their expression is differentially regulated by neuronal activities, suggesting that EPs may actively participate in hippocampal synaptic transmission and plasticity.