Inhibition of acid-sensing ion channels by levo-tetrahydropalmatine in rat dorsal root ganglion neurons.
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 pH0.5 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.
Institute of Ion Channels, Department of Pharmacology, Hubei University of Science and Technology, Hubei, People's Republic of China.
Ting-Ting
TT
Liu
Zu-Wei
ZW
Qu
Chun-Yu
CY
Qiu
Fang
F
Qiu
Cuixia
C
Ren
Xiong
X
Gan
Fang
F
Peng
Wang-Ping
WP
Hu
D062646:Acid Sensing Ion Channel Blockers / Q000494:pharmacology; D062565:Acid Sensing Ion Channels / Q000378:metabolism*; D000818:Animals; D001600:Berberine Alkaloids / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005727:Ganglia, Spinal / Q000166:cytology*; D006863:Hydrogen-Ion Concentration; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011522:Protons / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D062646:Acid Sensing Ion Channel Blockers; D062565:Acid Sensing Ion Channels; D001600:Berberine Alkaloids; D002121:Calcium Channel Blockers; D011522:Protons; C014215:tetrahydropalmatine
acid-sensing ion channel; dorsal root ganglion neuron; electrophysiology; levo-tetrahydropalmatine; pain