title: Inhibition of acid-sensing ion channels by chlorogenic acid in rat dorsal root ganglion neurons.
abstract: Chlorogenic acid (CGA) is one of the most abundant polyphenol compounds in the human diet. Recently, it is demonstrated to have potent antinociceptive effect. However, little is understood about the mechanism underlying CGA analgesia. Here, we have found that CGA can exert an inhibitory effect on the functional activity of native acid-sensing ion channels (ASICs) in rat dorsal root ganglion (DRG) neurons. First, CGA decreased the peak amplitude of proton-gated currents mediated by ASICs in a concentration-dependent manner. Second, CGA shifted the proton concentration-response curve downward, with a decrease of 41.76 ± 8.65% in the maximum current response to protons but with no significant change in the pH0.5 value. Third, CGA altered acidosis-evoked membrane excitability of rat DRG neurons and caused a significant decrease in the amplitude of the depolarization and the number of action potentials induced by acid stimuli. Finally, peripheral administered CGA attenuated nociceptive response to intraplantar injection of acetic acid in rats. ASICs are distributed in peripheral sensory neurons and participate in nociception. Our findings CGA inhibition of native ASICs indicated that CGA may exert analgesic action by modulating ASICs in the primary afferent neurons, which revealed a novel cellular and molecular mechanism underlying CGA analgesia.
authors.affiliation: Department of Pharmacology, Hubei University of Science and Technology, 88 Xianning Road, Xianning, 437100, Hubei, PR China.
authors.forename: Zu-Wei
authors.initials: ZW
authors.lastname: Qu
authors.affiliation: Department of Pharmacology, Hubei University of Science and Technology, 88 Xianning Road, Xianning, 437100, Hubei, PR China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Hubei University of Science and Technology, 88 Xianning Road, Xianning, 437100, Hubei, PR China.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Qiu
authors.affiliation: Department of Pharmacology, Hubei University of Science and Technology, 88 Xianning Road, Xianning, 437100, Hubei, PR China.
authors.forename: Jia-Da
authors.initials: JD
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Hubei University of Science and Technology, 88 Xianning Road, Xianning, 437100, Hubei, PR China. Electronic address: wangping_hu@163.com.
authors.forename: Wang-Ping
authors.initials: WP
authors.lastname: Hu
mesh_terms: D019342:Acetic Acid; D062646:Acid Sensing Ion Channel Blockers / Q000494:pharmacology*; D062565:Acid Sensing Ion Channels / Q000502:physiology*; D000200:Action Potentials; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D002726:Chlorogenic Acid / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D015640:Ion Channel Gating; D008297:Male; D059225:Nociception / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000502:physiology
chemical_list: D062646:Acid Sensing Ion Channel Blockers; D062565:Acid Sensing Ion Channels; D000700:Analgesics; D002726:Chlorogenic Acid; D019342:Acetic Acid
keywords: Acid-sensing ion channel; Chlorogenic acid; Dorsal root ganglion neuron; Pain; Proton-gated current