PPAR-α acutely inhibits functional activity of ASICs in rat dorsal root ganglion neurons
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Jing Wu1,*, Jia-Jia Wang1,*, Ting-Ting Liu1,2, Yi-Mei Zhou1, Chun-Yu Qiu3, Ding-Wen Shen1 and Wang-Ping Hu1,2
1Research Center of Basic Medical Sciences, School of Basic Medical Sciences, Hubei University of Science and Technology, Xianning 437100, Hubei, P.R. China
2Department of Physiology, School of Basic Medical Sciences, Hubei University of Science and Technology, Xianning 437100, Hubei, P.R. China
3Department of Pharmacology, Hubei University of Science and Technology, Xianning 437100, Hubei, P.R. China
*These authors have contributed equally to this work
Wang-Ping Hu, email: [email protected]
Keywords: peroxisome proliferator-activated receptor-α, acid-sensing ion channels, proton-gated current, nociception, dorsal root ganglion neuron
Received: April 05, 2017 Accepted: August 29, 2017 Published: October 10, 2017
Peroxisome proliferator-activated receptor-α (PPAR-α), a lipid activated transcription factor of nuclear hormone receptor superfamily, can relieve pain through a rapid-response mechanism. However, little is known about the underlying mechanism. Herein, we report that PPAR-α activation acutely inhibits the functional activity of acid-sensing ion channels (ASICs), key sensors for extracellular protons, in rat dorsal root ganglion (DRG) neurons. Pre-application of PPAR-α agonist GW7647 for 2 min decreased the amplitude of proton-gated currents mediated by ASICs in a concentration-dependent manner. GW7647 shifted the concentration-response curve for proton downwards, with a decrease of 36.9 ± 2.3% in the maximal current response to proton. GW7647 inhibition of proton-gated currents can be blocked by GW6471, a selective PPAR-α antagonist. Moreover, PPAR-α activation decreased the number of acidosis-evoked action potentials in rat DRG neurons. Finally, peripheral administration of GW7647 dose-dependently relieved nociceptive responses to injection of acetic acid in rats. These results indicated that activation of peripheral PPAR-α acutely inhibited functional activity of ASICs in a non-genomic manner, which revealed a novel mechanism underlying rapid analgesia through peripheral PPAR-α.
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