Inhibition of Acid-Sensing Ion Channels by Levo-Tetrahydropalmatine in Rat Dorsal Root Ganglion Neurons
Inhibition of Acid-Sensing Ion Channels by Levo-Tetrahydropalmatine in Rat Dorsal Root Ganglion Neurons
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DOI：
10.1002/jnr.23484
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发表时间：
2015-02-01
影响因子：
4.2
通讯作者：
Hu, Wang-Ping
中科院分区：
文献类型：
--
作者：
Liu, Ting-Ting;Qu, Zu-Wei;Hu, Wang-Ping
Levo-tetrahydropalmatine (l-THP), a main bioactive Chinese herbal constituent from the genera Stephania and Corydalis, has been in use in clinical practice for years in China as a traditional analgesic agent. However, the mechanism underlying the analgesic action of l-THP is poorly understood. This study shows that l-THP can exert an inhibitory effect on the functional activity of native acid-sensing ion channels (ASICs), which are believed to mediate pain caused by extracellular acidification. l-THP dose dependently decreased the amplitude of proton-gated currents mediated by ASICs in rat dorsal root ganglion (DRG) neurons. l-THP shifted the proton concentration-response curve downward, with a decrease of 40.93%+/- 8.45% in the maximum current response to protons, with no significant change in the pH(0.5) value. Moreover, l-THP can alter the membrane excitability of rat DRG neurons to acid stimuli. It significantly decreased the number of action potentials and the amplitude of the depolarization induced by an extracellular pH drop. Finally, peripherally administered l-THP inhibited the nociceptive response to intraplantar injection of acetic acid in rats. These results indicate that l-THP can inhibit the functional activity of ASICs in dissociated primary sensory neurons and relieve acidosis-evoked pain in vivo, which for the first time provides a novel peripheral mechanism underlying the analgesic action of l-THP. (c) 2014 Wiley Periodicals, Inc.
