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Mediators Inflamm. 2016;2016:5079597. doi: 10.1155/2016/5079597. Epub 2016 May 19.

An EP2 Agonist Facilitates NMDA-Induced Outward Currents and Inhibits Dendritic Beading through Activation of BK Channels in Mouse Cortical Neurons.

Author information

1
Department of Aging Science and Pharmacology, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan.
2
Department of Aging Science and Pharmacology, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Dental Anesthesiology, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan.
3
Department of Aging Science and Pharmacology, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan; Institute for Metabolic and Neuropsychiatric Disorders, Binzhou Medical University, Binzhou 256603, China.
4
Department of Dental Anesthesiology, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan.

Abstract

Prostaglandin E2 (PGE2), a major metabolite of arachidonic acid produced by cyclooxygenase pathways, exerts its bioactive responses by activating four E-prostanoid receptor subtypes, EP1, EP2, EP3, and EP4. PGE2 enables modulating N-methyl-D-aspartate (NMDA) receptor-mediated responses. However, the effect of E-prostanoid receptor agonists on large-conductance Ca(2+)-activated K(+) (BK) channels, which are functionally coupled with NMDA receptors, remains unclear. Here, we showed that EP2 receptor-mediated signaling pathways increased NMDA-induced outward currents (I NMDA-OUT), which are associated with the BK channel activation. Patch-clamp recordings from the acutely dissociated mouse cortical neurons revealed that an EP2 receptor agonist activated I NMDA-OUT, whereas an EP3 receptor agonist reduced it. Agonists of EP1 or EP4 receptors showed no significant effects on I NMDA-OUT. A direct perfusion of 3,5'-cyclic adenosine monophosphate (cAMP) through the patch pipette facilitated I NMDA-OUT, which was abolished by the presence of protein kinase A (PKA) inhibitor. Furthermore, facilitation of I NMDA-OUT caused by an EP2 receptor agonist was significantly suppressed by PKA inhibitor. Finally, the activation of BK channels through EP2 receptors facilitated the recovery phase of NMDA-induced dendritic beading in the primary cultured cortical neurons. These results suggest that a direct activation of BK channels by EP2 receptor-mediated signaling pathways plays neuroprotective roles in cortical neurons.

PMID:
27298516
PMCID:
PMC4889853
DOI:
10.1155/2016/5079597
[Indexed for MEDLINE]
Free PMC Article

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