Enhancement of acid-sensing ion channel activity by prostaglandin E2 in rat dorsal root ganglion neurons.

Abstract

Prostaglandin E2 (PGE2) and proton are typical inflammatory mediators. They play a major role in pain processing and hypersensitivity through activating their cognate receptors expressed in terminals of nociceptive sensory neurons. However, it remains unclear whether there is an interaction between PGE2 receptors and proton-activated acid-sensing ion channels (ASICs). Herein, we show that PGE2 enhanced the functional activity of ASICs in rat dorsal root ganglion (DRG) neurons through EP1 and EP4 receptors. In the present study, PGE2 concentration-dependently increased ASIC currents in DRG neurons. It shifted the proton concentration-response curve upwards, without change in the apparent affinity of proton for ASICs. Moreover, PGE2 enhancement of ASIC currents was partially blocked by EP1 or EP4 receptor antagonist. PGE2 failed to enhance ASIC currents when simultaneous blockade of both EP1 and EP4 receptors. PGE2 enhancement was partially suppressed after inhibition of intracellular PKC or PKA signaling, and completely disappeared after concurrent blockade of both PKC and PKA signaling. PGE2 increased significantly the expression levels of p-PKCε and p-PKA in DRG cells. PGE2 also enhanced proton-evoked action potentials in rat DRG neurons. Finally, peripherally administration of PGE2 dose-dependently exacerbated acid-induced nocifensive behaviors in rats through EP1 and EP4 receptors. Our results indicate that PGE2 enhanced the electrophysiological activity of ASICs in DRG neurons and contributed to acidosis-evoked pain, which revealed a novel peripheral mechanism underlying PGE2 involvement in hyperalgesia by sensitizing ASICs in primary sensory neurons.

• Authors: Yi-Mei Zhou, Lei Wu, Shuang Wei, Ying Jin, Ting-Ting Liu, Chun-Yu Qiu, Wang-Ping Hu
• Journal: Brain research (Brain Res) Vol. 1724 Pg. 146442 (12 01 2019) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 31513790 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Acid Sensing Ion Channels
• Receptors, Prostaglandin E, EP2 Subtype
• Receptors, Prostaglandin E, EP4 Subtype
• Dinoprostone

Topics

• Acid Sensing Ion Channels (metabolism, physiology)
• Action Potentials (drug effects)
• Animals
• Dinoprostone (metabolism, physiology)
• Ganglia, Spinal (metabolism)
• Hyperalgesia (metabolism)
• Male
• Neurons (metabolism)
• Nociceptors (metabolism)
• Pain (physiopathology)
• Pain Measurement (drug effects)
• Rats
• Rats, Sprague-Dawley
• Receptors, Prostaglandin E, EP2 Subtype (metabolism, physiology)
• Receptors, Prostaglandin E, EP4 Subtype (metabolism)
• Sensory Receptor Cells (drug effects)
• Signal Transduction (drug effects)