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 wholecell 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 TRPA1antagonists. 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 Ad-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 Ad-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.

Ligand‐stereoselective allosteric activation of cold‐sensing TRPM8 channels by an H‐bonded homochiral menthol dimer with head‐to‐head or head‐to‐tail

“…59,71,79,80 It has also been reported that the substantia gelatinosa neurons in the presence of TRPV1 or TRPA1 or TRPM8 channels show a high degree of stereoselectivity and the high Hill coefficient of a dose response towards several classes of plant-derived menthol derivative chemical stereoisomers. They include thymol and carvacrol (C 10 H 14 O, 5-isopropyl-2-methylphenol), (À)-carvone (C 10 H 14 O, (À)-2-methyl- 71,[81][82][83][84][85] Therefore, it is promising to investigate if an H-bonded homochiral dimer or pair with side-or tandem-connected head-to-head or tail-totail or head-to-tail plays a pivotal role in discriminating stereoisomers for allosteric activation of those TRP channels.…”

Role of phytochemicals as nutraceuticals for cognitive functions affected in ageing

“…‐Modulates TRP (transient receptor potential) channels (including increasing spontaneous glutamate release); dysregulation of which have been suggested to be involved in neurological and psychiatric disorders (Jiang et al, )…”

Differential Activation of TRP Channels in the Adult Rat Spinal Substantia Gelatinosa by Stereoisomers of Plant-Derived Chemicals

“…The SG neurons play a pivotal role in modulating nociceptive transmission from the periphery [ 24 , 25 , 26 ] and thus TRP channels in the SG are involved in its modulation. Their expressions in the SG have been shown by immunohistochemistry [ 27 ].…”

“…The thymol activity was inhibited by a TRPA1 antagonist HC-030031 (50 μM; [ 95 ]) but not a TRPV1 antagonist capsazepine (10 μM; [ 96 ]) and a TRPM8 antagonist (4-(3-chloro-2-pyridinyl)- N -[4-(1,1-dimethyl-ethyl)phenyl]-1-piperazinecarboxamide, BCTC, 3 μM; [ 97 ]; Figure 1 E). BCTC at this concentration was effective in inhibiting sEPSC frequency increase produced by menthol in adult rat SG neurons [ 27 ]. As with thymol, the carvacrol activity was resistant to capsazepine (10 μM) while being depressed by HC-030031 (50 μM; Figure 1 F).…”

“…The presynaptic activities of 1,8-cineole and 1,4-cineole were not accompanied by the production of outward current, as different from those of thymol and carvacrol. As with many kinds of TRPV1 and TRPA1 agonists [ 15 , 18 , 19 ] including (−)-carvone and (+)-carvone, 1,8-cineole and 1,4-cineole produced a small inward current ( Figure 3 E,F; [ 27 ]).…”