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Mediators of Inflammation
Volume 2016, Article ID 5079597, 9 pages
http://dx.doi.org/10.1155/2016/5079597
Research Article

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

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

Received 26 February 2016; Revised 19 April 2016; Accepted 4 May 2016

Academic Editor: Hermann Gram

Copyright © 2016 Yoshinori Hayashi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 Ca2+-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 (), 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 , whereas an EP3 receptor agonist reduced it. Agonists of EP1 or EP4 receptors showed no significant effects on . A direct perfusion of 3,5′-cyclic adenosine monophosphate (cAMP) through the patch pipette facilitated , which was abolished by the presence of protein kinase A (PKA) inhibitor. Furthermore, facilitation of 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.