title: Carvacrol presynaptically enhances spontaneous  excitatory transmission and produces outward  current in adult rat spinal substantia  gelatinosa neurons.
abstract: Carvacrol, which is abundantly contained in oregano essential oils, has various pharmacological actions including antinociception. Although the oral administration of carvacrol results in antinociception, cellular mechanisms for this action have not been examined yet. We investigated the action of carvacrol on glutamatergic spontaneous excitatory transmission in substantia gelatinosa neurons which play a pivotal role in regulating nociceptive transmission from the periphery by using the patch-clamp technique in adult rat spinal cord slices. Carvacrol superfused for 2 min produced either spontaneous excitatory postsynaptic current frequency increase or outward current at −70 mV, or both of them in many of the neurons tested. The frequency increase and outward current had the EC(50) values of 0.69 mM and 0.55 mM, respectively. The former action was inhibited by a selective TRPA1 antagonist HC-030031 but not a selective TRPV1 antagonist capsazepine, while the latter action was unaffected by their antagonists. The current–voltage relationship for the outward current indicated an involvement in the current of a change in the membrane permeability of K(+) and its outward rectification. The outward current was inhibited in 10 mM-K((+) 0but not K(+)-channel blockers [tetraethylammonium and Ba(2+)]-containing and 11.0 mM-Cl- Krebs solution. These results indicate that carvacrol increases the spontaneous release of l-glutamate from nerve terminals by activating TRPA1 but not TRPV1 channels and produces membrane hyperpolarization, which is possibly mediated by tetraethylammonium- and Ba(2+)-insensitive K(+) channels, in substantia gelatinosa neurons. It is suggested that the hyperpolarizing effect of carvacrol could contribute to its antinociceptive action.
authors.forename: Qing-Tian
authors.initials: QT
authors.lastname: Luo
authors.forename: Tsugumi
authors.initials: T
authors.lastname: Fujita
authors.forename: Chang-Yu
authors.initials: CY
authors.lastname: Jiang
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kumamoto
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D000081007:Cymenes; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D039821:Monoterpenes / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D059225:Nociception / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D010539:Permeability / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D013376:Substantia Gelatinosa / Q000187:drug effects* / Q000502:physiology; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D000700:Analgesics; D000081007:Cymenes; D018683:Excitatory Amino Acid Agents; D039821:Monoterpenes; D018377:Neurotransmitter Agents; D026902:Potassium Channel Blockers; D011687:Purines; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050916:TRPV Cation Channels; C480976:Trpa1 protein, rat; C493922:Trpv1 protein, rat; D018698:Glutamic Acid; C073316:carvacrol; C071423:capsazepine; D011188:Potassium; D002211:Capsaicin