title: 1,8- and 1,4-cineole enhance spontaneous excitatory transmission by activating different types of transient receptor potential channels in the rat spinal substantia gelatinosa.
abstract: Although transient receptor potential (TRP) channels expressed in the spinal substantia gelatinosa play a role in modulating nociceptive transmission, their properties have not been fully examined yet. In order to address this issue, the effects of 1,8-cineole and its stereoisomer 1,4-cineole on excitatory transmission were examined by applying the whole-cell patch-clamp technique to substantia gelatinosa neurons in adult rat spinal cord slices. Miniature excitatory postsynaptic current frequency was increased by 1,8- and 1,4-cineole. The cineole activities were repeated and resistant to voltage-gated Na+-channel blocker tetrodotoxin. The 1,8-cineole activity was inhibited by TRP ankyrin-1 (TRPA1) antagonists (HC-030031 and mecamylamine) but not TRP vanilloid-1 (TRPV1) antagonists (capsazepine and SB-366791), whereas the 1,4-cineole activity was depressed by the TRPV1 but not TRPA1 antagonists. Although 1,8- and 1,4-cineole reportedly activate TRP melastatin-8 (TRPM8) channels, their activities were unaffected by TRPM8 antagonist 4-(3-chloro-2-pyridinyl)-N-[4-(1,1-dimethylethyl)phenyl]-1-piperazinecarboxamide. Monosynaptically evoked C-fiber, but not Aδ-fiber excitatory postsynaptic current amplitude, was reduced by 1,8- and 1,4-cineole. These results indicate that 1,8- and 1,4-cineole increase spontaneous l-glutamate release from nerve terminals by activating TRPA1 and TRPV1 channels, respectively, while inhibiting C-fiber but not Aδ-fiber evoked l-glutamate release. This difference between 1,8- and 1,4-cineole may serve to know the properties of TRP channels located in the central terminals of primary-afferent neurons. The spinal dorsal horn lamina II (substantia gelatinosa; SG) plays a pivotal role in regulating nociceptive transmission from the periphery. We found out in the SG that 1,4- and 1,8-cineole activate TRPV1 and TRPA1 channels, respectively, located in primary-afferent, possibly C-fiber, central terminals. This difference may serve to know the properties of TRP channels expressed in the central terminals.
authors.affiliation: Department of Physiology, Saga Medical School, Saga, Japan.
authors.forename: Chang-Yu
authors.initials: CY
authors.lastname: Jiang
authors.affiliation: Department of Physiology, Saga Medical School, Saga, Japan.
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Physiology, Saga Medical School, Saga, Japan.
authors.forename: Nian-Xiang
authors.initials: NX
authors.lastname: Xu
authors.affiliation: Department of Physiology, Saga Medical School, Saga, Japan.
authors.forename: Tsugumi
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Department of Anatomy, Saga Medical School, Saga, Japan.
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Murata
authors.affiliation: Department of Physiology, Saga Medical School, Saga, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kumamoto
keywords: TRPA1; TRPV1; cineole; excitatory transmission; spinal substantia gelatinosa; whole-cell patch-clamp