title: Enhancement by citral of glutamatergic spontaneous excitatory transmission in adult rat substantia gelatinosa neurons.
abstract: Although citral, which is abundantly present in lemongrass, has various actions including antinociception, how citral affects synaptic transmission has not been examined as yet. Citral activates in heterologous cells transient receptor potential vanilloid-1, ankyrin-1, and melastatin-8 (TRPV1, TRPA1, and TRPM8, respectively) channels, the activation of which in the spinal lamina II [substantia gelatinosa (SG)] increases the spontaneous release of L-glutamate from nerve terminals. It remains to be examined what types of transient receptor potential channel in native neurons are activated by citral. With a focus on transient receptor potential activation, we examined the effect of citral on glutamatergic spontaneous excitatory transmission using the whole-cell patch-clamp technique to SG neurons in adult rat spinal cord slices. Bath-applied citral for 3 min increased the frequency of spontaneous excitatory postsynaptic current in a concentration-dependent manner (half-maximal effective concentration=0.58 mM), with a small increase in its amplitude. The spontaneous excitatory postsynaptic current frequency increase produced by citral was repeated at a time interval of 30 min, albeit this action recovered with a slow time course after washout. The presynaptic effect of citral was inhibited by TRPA1 antagonist HC-030031, but not by voltage-gated Na-channel blocker tetrodotoxin, TRPV1 antagonist capsazepine, and TRPM8 antagonist BCTC. It is concluded that citral increases spontaneous L-glutamate release in SG neurons by activating TRPA1 channels. Considering that the SG plays a pivotal role in modulating nociceptive transmission from the periphery, the citral activity could contribute toward at least a part of the modulation.
authors.affiliation: Department of Physiology, Saga Medical School, Nabeshima, Saga, Japan.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhu
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: D000080462:Acyclic Monoterpenes; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D018698:Glutamic Acid / Q000187:drug effects*; D039821:Monoterpenes / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013376:Substantia Gelatinosa / Q000187:drug effects*; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000187:drug effects*; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors / Q000187:drug effects; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000187:drug effects
chemical_list: D000080462:Acyclic Monoterpenes; D039821:Monoterpenes; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050053:TRPM Cation Channels; D050916:TRPV Cation Channels; C480976:Trpa1 protein, rat; C498947:Trpm8 protein, rat; C493922:Trpv1 protein, rat; D018698:Glutamic Acid; C007076:citral