Heterogeneous expression and regulation of hippocampal prostaglandin E2 receptors

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Abstract
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, EP1–4, were detected both in the hippocampus and in the neocortex. EP2 and EP3 appeared in greater abundance, whereas EP1 and EP4 were barely detectable. EP1, EP2 and EP4 were mainly colocalized with synaptophysin, suggesting the presence of EP1, EP2, and EP4 in presynaptic terminals. It appeared that interleukin-1β increased the expression of EP2 and EP4 mRNAs. A blockade of synaptic transmission with either tetrodotoxin or MK-801 plus 6,7-dinitroquinoxaline-2,3-dione (DNQX) for 6 hr increased EP3 and EP4 mRNA, whereas high K+ (90 mM) or 4-aminopyridine enhanced EP2 and EP4. The EP1 level did not change significantly under these conditions. The expressions of EP2, EP4, and EP3 were further elevated or reduced in neurons treated with high K+ for 24 hr. However, mRNA of EP3 was down-regulated in neurons treated with tetrodotoxin or MK-801 plus DNQX for 24 hr. In addition, both EP2 and EP4 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.