1. Academic Validation
  2. Lipid mediator resolvin D2 inhibits ATP currents in rat primary sensory neurons

Lipid mediator resolvin D2 inhibits ATP currents in rat primary sensory neurons

  • J Neurochem. 2023 Nov 21. doi: 10.1111/jnc.16009.
Jia-Wei Hao 1 Ting-Ting Liu 1 Chun-Yu Qiu 1 Xue-Mei Li 1 Wen-Long Qiao 1 Qing Li 1 Qing-Rui Qin 1 Wang-Ping Hu 1 2
Affiliations

Affiliations

  • 1 School of Pharmacy, School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei, PR China.
  • 2 Department of Physiology, Hubei College of Chinese Medicine, Jingzhou, Hubei, PR China.
Abstract

Resolvin D2 (RvD2), an endogenous lipid mediator derived from docosahexaenoic acid, has been demonstrated to have analgesic effects. However, little is known about the mechanism underlying RvD2 in pain relief. Herein, we demonstrate that RvD2 targeted the P2X3 Receptor as an analgesic. The electrophysiological activity of P2X3 receptors was suppressed by RvD2 in rat dorsal root ganglia (DRG) neurons. RvD2 pre-application dose-dependently decreased α,β-methylene-ATP (α,β-meATP)-induced inward currents. RvD2 remarkably decreased the maximum response to α,β-meATP, without influencing the affinity of P2X3 receptors. RvD2 also voltage-independently suppressed ATP currents. An antagonist of the G protein receptor 18 (GPR18), O-1918, prevented the RvD2-induced suppression of ATP currents. Additionally, intracellular dialysis of the Gαi/o -protein antagonist pertussis toxin (PTX), the PKA antagonist H89, or the cAMP analog 8-Br-cAMP also blocked the RvD2-induced suppression. Furthermore, α,β-meATP-triggered depolarization of membrane potential along with the action potential bursts in DRG neurons were inhibited by RvD2. Lastly, RvD2 attenuated spontaneous nociceptive behaviors as well as mechanical allodynia produced by α,β-meATP in rats via the activation of the peripheral GPR18. These findings indicated that RvD2 inhibited P2X3 receptors in rat primary sensory neurons through GPR18, PTX-sensitive Gαi/o -proteins, and intracellular cAMP/PKA signaling, revealing a novel mechanism that underlies its analgesic effects by targeting P2X3 receptors.

Keywords

P2X3 receptor; Resolvin D2; current; dorsal root ganglion neuron; nociceptive behavior.

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