Novel agonistic action of mustard oil on recombinant and endogenous porcine transient receptor potential V1 (pTRPV1) channels.
Neurogenic components play a crucial role in inflammation and nociception. Mustard oil (MO) is a pungent plant extract from mustard seed, horseradish and wasabi, the main constituent of which is allylisothiocyanate. We have characterized the action of MO on transient receptor potential V1 (TRPV1), a key receptor of signal transduction pathways in the nociceptive system, using fura-2-based [Ca(2+)](i) imaging and the patch-clamp technique in a heterologous expression system and sensory neurons. In human embryonic kidney (HEK) 293 cells expressing porcine TRPV1 (pTRPV1), MO evoked increases of [Ca(2+)](i) in a concentration-dependent manner. A high concentration of MO elicited irreversible cell swelling. Capsazepine, ruthenium red and iodoresiniferatoxin dose-dependently suppressed the MO-induced [Ca(2+)](i) increase. MO elicited outward rectified currents in pTRPV1-expressing HEK 293 cells with a reversal potential similar to that of capsaicin. [Ca(2+)](i) responses to MO were completely abolished by the removal of external Ca(2+). MO simultaneously elicited an inward current and increase of [Ca(2+)](i) in the same cells, indicating that MO promoted Ca(2+) influx through TRPV1 channels. In cultured porcine dorsal root ganglion (DRG) neurons, MO elicited a [Ca(2+)](i) increase and inward current. Among DRG neurons responding to MO, 85% were also sensitive to capsaicin. The present data indicate that MO is a novel agonist of TRPV1 channels, and suggest that the action of MO in vivo may be partly mediated via TRPV1. These results provide an insight into the TRPV1-mediated effects of MO on inflammation and hyperalgesia.
Ohta
Toshio
T
Laboratory of Pharmacology, Department of Biochemical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan. tohta@vetmed.hokudai.ac.jp
Imagawa
Toshiaki
T
Ito
Shigeo
S
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D009149:Mustard Plant; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010938:Plant Oils / Q000494:pharmacology*; D051381:Rats; D011994:Recombinant Proteins / Q000819:agonists*; D034421:Sus scrofa; D013552:Swine; D050916:TRPV Cation Channels / Q000819:agonists*
D010938:Plant Oils; D011994:Recombinant Proteins; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium; C027793:mustard oil