Inhibitory effect of cochinchinenin B on capsaicin-activated responses in rat dorsal root ganglion neurons.
Vanilloid receptor 1 (VR1) is a noxious receptor and a novel target for pain therapy. Cochinchinenin B (6-hydroxy-7-methoxy-3-(4'-hydroxybenzyl) chromone; CB) is one of the small-molecular components from the flavonoids of Dragon's Blood, a well-known herbal medicine to treat various types of pain. Using whole-cell patch clamp technique, we found that capsaicin (CAP)-activated currents (ICAP) was inhibited by CB with an IC50 of 0.92 mM in acutely isolated rat dorsal root ganglion (DRG) neurons. The inhibition was reversible and not competitive. We also found that the inhibition was neither voltage- nor agonist-dependent. The bind site was on the extracellular part of the channel since intracellular application of CB did not alter the inhibition effect on ICAP. In addition, CB inhibited CAP-evoked depolarization under current-clamp condition. Our findings indicate that CB may be a candidate in developing new analgesic drugs targeting the VR1 receptor.
Wang
Song-tao
ST
Department of Biomedical Engineering, Wuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities, Wuhan 430074, China.
Chen
Su
S
Guo
Min
M
Liu
Xiang-ming
XM
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002478:Cells, Cultured; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D015394:Molecular Structure; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000037:antagonists & inhibitors; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000700:Analgesics; D004365:Drugs, Chinese Herbal; D018689:Sensory System Agents; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C475447:cochinchinenin; D002599:Chalcone; D002211:Capsaicin