ライフサイエンスコーパス: menthol

1 hannels with augmented responses to cold and menthol.

2 d are required for the inhibition of itch by menthol.

3 arable increase in the responses to cold and menthol.

4 , phosphatidylinositol 4,5-bisphosphate, and menthol.

5 of DRG neurons respond to the TRPM8 agonist menthol.

6 rees C-20 degrees C) and oral sensitivity to menthol.

7 so underlies the species-specific effects of menthol.

8 vated by cold and cooling compounds, such as menthol.

9 anner when activated by the cooling compound menthol.

10 from nonmammalian species are insensitive to menthol.

11 mice (TRPM8(EGFPf/+)) responded to cold and menthol.

12 the activation of TRPM8 by cold, icilin, and menthol.

13 icin and the activation of TRPM8 channels by menthol.

14 neurons by cold or by cooling agents such as menthol.

15 recombinant TRPM8 channels by both cold and menthol.

16 remain responsive to touch, temperature, and menthol.

17 nd no additional effect of including chronic menthol.

18 rons that are activated by the cooling agent menthol.

19 ffecting actions of A-967079 or the agonist, menthol.

20 s after corneal application of capsaicin and menthol.

21 type and knockout mice after application of menthol (0.05-50 mM) to the cornea.

22 A low concentration of menthol (0.1 mM) increased cool cell activity, yet a hig

23 15 degrees C and 39 degrees C-51 degrees C), menthol (10-100 microM), and hyperosmolar solutions (NaC

24 eurons responding to cold (18 degrees C) and menthol (100 microM) is greatly decreased.

25 minant compounds were cis-menthone (27.43%), menthol (24.3%), trans-menthone (9.23%), limonene (5.84%

26 mproved the chiral purity of the contained d-menthol (3), an example of purification by "duplication"

27 iral terpene alcohols, including d- (3) or l-menthol (4), d-isomenthol (7), l-borneol (8), or d- (5)

28 l pyromellitate triacid chloride (30) with l-menthol (4).

29 l cell activity, yet a high concentration of menthol (50 mM) had no effect.

30 At the highest concentration, menthol (50 mM) increased tearing and nocifensive respon

31 (10 microm), resiniferatoxin (5 microm) and menthol (6 mm) reveal voltage-independent gating.

32 amined the effects of chronic treatment with menthol, a major flavor additive in tobacco cigarettes a

33 Menthol, a natural nonreactive cooling compound, is best

34 Menthol, a TRPM8 agonist, was ineffective at increasing

35 Menthol, a widely used additive in cigarettes, is a pote

36 Notably, menthol acted in a voltage-independent manner and reduce

37 ow that this effect is unlikely to arise via menthol actions on alpha3beta4 nAChRs.

38 The natural compounds capsaicin and menthol activate noxious heat-sensitive TRPV1 and cold-s

39 The cold- and menthol-activated ion channel transient receptor potenti

40 The cold- and menthol-activated transient receptor potential melastati

41 The activity of the cold- and menthol-activated transient receptor potential melastati

42 Ca(2+) signal and the prompt inactivation of menthol-activated transient receptor potential melastati

43 Here we investigated the mechanism by which menthol activates mouse TRPM8.

44 To understand how menthol activates the channel, we docked menthol to the

45 Menthol activates transient receptor potential melastati

46 stand' mechanism of menthol binding and how menthol activates TRPM8 at the atomic level.

47 ngly shifted the concentration dependence of menthol activation, raising the possibility that S2 infl

48 n of the trioxatricornan with amino acids or menthol afforded diastereomers that were resolved by pre

49 Menthol, AITC, and capsaicin also elicited robust calciu

50 and the active ingredients of these plants - menthol, allyl isothiocyanate (AITC), and capsaicin, res

51 uorescent nAChR subunits, exposure to 500 nm menthol alone also increased nAChR number and favored th

52 Menthol alone also increases the number of alpha6beta2 r

53 mice containing fluorescent nAChR subunits, menthol alone increased the number of alpha4 and alpha6

54 We investigated the effect of long-term menthol alone on midbrain neurons containing nAChRs.

55 's effects were not specific to acrolein, as menthol also attenuated irritation responses to acetic a

56 Menthol also enhances nicotine-induced changes in DA neu

57 , and Ca(2+), as well as in complex with the menthol analog WS-12 and PIP(2) Our structures reveal th

58 nyl of menthone is reduced to yield (-)-(3R)-menthol and (+)-(3S)-neomenthol by two distinct NADPH-de

59 D and converts (-)-menthone to 95% (-)-(3R)-menthol and 5% (+)-(3S)-neomenthol, and (+)-isomenthone

60 In a counter-balanced cross-over design, 10 menthol and 9 non-menthol smokers (10 females and 9 male

61 nents that include thymol, citral, linalool, menthol and borneol.

62 We found that menthol and capsaicin both caused a significant reductio

63 d intensity perception of sucrose, caffeine, menthol and capsaicin solutions.

64 ons initiated by sweat-triggered ejection of menthol and capsaicin.

65 he emerging interpretation that both chronic menthol and chronic nicotine act on nAChRs in the early

66 Two commercially available alcohols, L-menthol and citronellol, were coupled to the AB(2) monom

67 erature activation and a reduced response to menthol and cold stimuli.

68 the channel activity, sensitivity to icilin, menthol and cold, and impact on channel oligomerization.

69 These experiments demonstrate that menthol and eucalyptol, through activation of TRPM8, act

70 TRPM8 channel behavior upon menthol and icilin activation was distinguishable, and t

71 vated by cold and chemical agonists, such as menthol and icilin.

72 RPM8 is also activated by the cooling agents menthol and icilin.

73 found that membrane currents evoked by both menthol and innocuous cold were significantly enhanced i

74 the responsiveness of these neurons to both menthol and innocuous cold.

75 ld thermosensors are uniformly responsive to menthol and innocuous cool temperature (17 degrees C), i

76 uding natural products such as alpha-pinene, menthol and limonene.

77 Menthol and many of its derivatives produce profound sen

78 tential of major cyclic oxygenated terpenes (menthol and menthone) are conflicting.

79 We found that the HIPVs menthol and methyl salicylate at 1 and 10 nmol.ml(-1) im

80 ve (AUC), and T1/2 of BNA were found between menthol and non-menthol cigarettes across all subjects;

81 idence for differential associations between menthol and nonmenthol cigarettes indicates lower cancer

82 Menthol and other counterstimuli relieve itch, resulting

83 ereogenic compounds: Heating H3 PO2 with (-)-menthol and paraformaldehyde gives easily crystallized m

84 red in one step from naturally occurring (-)-menthol and readily available 1,2,3,4,5-pentacarbomethox

85 The nonelectrophilic compounds menthol and the cannabinoid Delta(9)-tetrahydrocannabior

86 -positive dorsal root ganglion neurons cold, menthol and WS-12, a selective TRPM8 agonist, evoked sig

87 64") that were 30 times (menthol) and 100 times (ethyl maltol) their cytotoxic co

88 me Brulee, Cool Cucumber, Mango, and Classic Menthol) and similar pod flavors (Just Mango-Strawberry

89 ng the neurons that are altered by nicotine, menthol, and acetylcholine.

90 afferent neurons also respond to capsaicin, menthol, and/or mustard oil (allyl isothiocyanate) at co

91 in-sensitive neurons increased, and that the menthol- and cold-evoked responses were significantly en

92 d in the regulation of TRPM8 channels during menthol- and cold-induced desensitization in vitro.

93 TRPM8, a cloned menthol- and cold-sensitive ion channel, has been sugges

94 a significant increase in the percentage of menthol- and cold-sensitive neurons and also a substanti

95 In small PLCdelta4(-/-) neurons, menthol application induced larger depolarizations and g

96 id closure) were quantified following cornea menthol application.

97 activated by noxious thermal stimulation and menthol applied to the corneal surface.

98 ome products had concentrations of menthol ("Menthol Arctic") and ethyl maltol ("No.

99 the cold-sensitizing effects of camphor and menthol are additive.

100 shment of protocols to regulatory the use of menthol as an anesthetic in aquaculture.

101 ound impact on channel gating by voltage and menthol, as evidenced by the modulation of the conductan

102 Moreover, menthol at concentrations up to 1 mM did not compete for

103 Menthol, at a concentration (16 ppm) lower than in smoke

104 Menthol attenuated the responses in all classes of therm

105 thermoreceptors and orosensory nociceptors; menthol attenuates cool thermoresponses.

106 7]helicene are obtained via resolution using menthol-based chiral siloxanes.

107 This platform was also expanded beyond menthol-based substrates to the selective hydroxylation

108 dy suggested a 'grab and stand' mechanism of menthol binding and how menthol activates TRPM8 at the a

109 orescent unnatural amino acid, we found that menthol binding induces wide-spread conformational rearr

110 the channel and systematically validated our menthol binding models with thermodynamic mutant cycle a

111 1008), but was independent of the icilin and menthol binding site residue Y745 and, essentially, the

112 , raising the possibility that S2 influences menthol binding.

113 The structure suggests that the menthol-binding site is located within the voltage-senso

114 noterpene reductases of mint involved in (-)-menthol biosynthesis.

115 termined in the apo and liganded states, the menthol-bounded state is unresolved.

116 ons of tacrolimus on TRPM8 resemble those of menthol but likely involve interactions with other chann

117 muM) and a similar efficacy when compared to menthol; by contrast, compound 12 produced a concentrati

118 ] as the critical domain determining whether menthol can act as an inhibitor.

119 Taken together, our results indicate that menthol can act directly on presynaptic Ca2+ stores of s

120 from a natural chiral pool of (1R,2S,5R)-(-)-menthol can be efficiently prepared by two different met

121 studies indicated that low concentrations of menthol can increase lacrimation via TRPM8 channels with

122 At high concentrations, menthol can induce lacrimation and nocifensive behaviors

123 We used concentrations of menthol, capsaicin, and hypertonic saline that evoked co

124 we show that B5-I neurons are innervated by menthol-, capsaicin-, and mustard oil-responsive sensory

125 and phenols, four natural products (eugenol, menthol, cholesterol, and estrone) were labeled in a sim

126 the protocol is suitable for even protecting menthol, cholesterol, serine, disaccharide OH, and furan

127 examples of increasing spectral complexity, menthol, cholesteryl acetate and a C(16) fatty acid, dem

128 n several aspects of nicotine addiction, and menthol cigarette smokers tend to upregulate beta2* nACh

129 /2 of BNA were found between menthol and non-menthol cigarettes across all subjects; however, menthol

130 alth, but these results do not indicate that menthol cigarettes are associated with greater CVD risks

131 Menthol cigarettes are likely associated with greater ri

132 es than whites, raising the possibility that menthol cigarettes contribute to racial disparities in r

133 behavior and may help explain how smokers of menthol cigarettes exhibit reduced cessation rates.

134 rstanding why the quit rate among smokers of menthol cigarettes is lower than non-menthol smokers req

135 king and preference of sensory properties of menthol cigarettes may independently or jointly contribu

136 In contrast to whites, black smokers prefer menthol cigarettes over nonmenthol cigarettes by a large

137 l subjects; however, menthol relative to non-menthol cigarettes were associated with steeper initial

138 greater risks of smoking dependence than non-menthol cigarettes.

139 ntervals for all-cause and CVD mortality for menthol compared with nonmenthol cigarette smokers among

140 .03; P=0.10) mortality risks were similar in menthol compared with nonmenthol cigarette smokers.

141 thol treatment at 500 nM, near the estimated menthol concentration in the brain following cigarette s

142 aging study on DRG neurons demonstrated that menthol could directly release Ca2+ from intracellular C

143 tch recordings from DRG-DH pairs showed that menthol could potentiate evoked EPSCs (eEPSCs) and chang

144 ning and cooling perception of capsaicin and menthol demonstrate that these ion channels mediate ther

145 A suite of menthol derivatives was screened computationally and eva

146 ersion of the protocol was explored with (L)-menthol derived nonracemic substrates, and the correspon

147 ine) and trapping with Andersen's sulfinate (menthol derived).

148 An analogous preparation of menthol-derived phosphinite boranes is also described.

149 keleton rearrangement was observed using the menthol-derived substrate.

150 r enantiomer of Andersen's readily available menthol-derived sulfinate or the alpha-alkylation of ena

151 vity of ACh-evoked currents, suggesting that menthol does not change alpha3beta4 nAChR subunit stoich

152 2 degrees C to higher temperatures, and the menthol dose-response curve was displaced to lower conce

153 first sensory synapse in the CNS, we studied menthol effects on sensory synaptic transmission and the

154 ably, TRP domain mutations mainly attenuated menthol efficacy, suggesting that this domain influences

155 Using mouse models, we show that menthol enhances nicotine-induced changes in nicotinic a

156 ll-diameter Vglut3(lineage) DRG neurons fire menthol-evoked action potentials and exhibited robust, t

157 ns in PIP2 had a similar effect on cold- and menthol-evoked currents.

158 jury, the percentage of CCSNs, the cold- and menthol-evoked intracellular [Ca(2+)] rises and the TRPM

159 ral opening and an increase in capsaicin and menthol-evoked responses only in female mice.

160 ds to adaptation-like reductions in cold- or menthol-evoked TRPM8 currents in both heterologous and n

161 we show that activation of TRPM8 by cold or menthol evokes a decrease in cellular phosphatidylinosit

162 Furthermore, menthol exposure before nicotine abolished nicotine rewa

163 mbustion process, the TPM from e-cigarettes (menthol flavor of NJOY and V2 brands) also contain EPFRs

164 oduct, glucan concentrations in tobacco- and menthol-flavored ECs were 10.4 (95% CI: 1.8, 44.9) and 3

165 Pretreatment with menthol followed by its washout did not affect agonist-i

166 elds 94% (+)-(3S)-neomenthol and 6% (-)-(3R)-menthol from (-)-menthone as substrate, and 86% (+)-(3S)

167 s were classified into four groups: tobacco, menthol, fruit, and other.

168 e that neurons expressing TRPM8, a cold- and menthol-gated channel required for normal cold responses

169 ly folded assembly domain from the cold- and menthol-gated channel TRPM8.

170 t al. report that mice lacking the cold- and menthol-gated ion channel TRPM8 exhibit deficient behavi

171 -inflammatory drugs (NSAIDs) with or without menthol gel as first-line therapy to reduce or relieve s

172 The receptor for menthol has been cloned and named cold- and menthol-sens

173 More recently, menthol has been shown to be an activator of mouse TRPA1

174 Furthermore, as menthol has been used for centuries as an analgesic and

175 oling (<28 degrees C) and cooling compounds (menthol, icilin) and are implicated in sensing unpleasan

176 ivated by a wide range of stimuli, including menthol, icilin, and cold temperatures (<25 degrees C).

177 It is highly controversial whether menthol in cigarette smoke exerts pharmacological action

178 vide strong support for the putative role of menthol in enhancing BNA, although further studies shoul

179 lied to residual determination of anesthetic menthol in fish.

180 as the primary molecular sensor of cold and menthol in humans.

181 Menthol in mints elicits coolness sensation by selective

182 residual period for total metabolization of menthol in the fishes' organisms.

183 At low concentrations, menthol increased tear production in TRPM8 wild type and

184 We found that menthol increased the frequency of miniature EPSCs (mEPS

185 avour components of peppermint (menthone and menthol) increased, while the contents of the main const

186 Menthol increases the potency of PI(4,5)P(2) to activate

187 We sought to test the hypothesis that menthol increases the rate of brain nicotine accumulatio

188 Menthol-induced Ca2+ release was abolished by 2-APB but

189 ts connect changes in midbrain DA neurons to menthol-induced enhancements of nicotine reward-related

190 Menthol-induced increases of mEPSC frequency were blocke

191 d to capsaicin, and had significantly larger menthol-induced inward current densities than medium-lar

192 uced a concentration-dependent inhibition of menthol-induced TRPM8 currents (IC50 = 367 +/- 24 nM).

193 urpose of our study was to determine whether menthol induces corneal cool cell activity and lacrimati

194 o entry into slow inactivation compared with menthol-insensitive neurons.

195 gher evoked firing frequencies compared with menthol-insensitive Vglut3(lineage) neurons.

196 f these mutants indicated that activation by menthol involves a gating mechanism distinct and separab

197 Menthol is a cooling compound derived from mint leaves a

198 We conclude that menthol is more than a tobacco flavorant: administered a

199 cold, voltage, and cooling compounds such as menthol, is the principal molecular detector of cold tem

200 e menthone reductases account for all of the menthol isomers found in the essential oil of peppermint

201 nces, we classify agonists as either type I (menthol-like) or type II (AITC-like), and provide a kine

202 We also found that menthol--like camphor--potently inhibits Kv7.2/3 channel

203 Menthol markedly decreased nAChR activity as assessed by

204 rough suppression of respiratory irritation, menthol may facilitate smoke inhalation and promote nico

205 -(13)C residual dipolar couplings (RDCs) for menthol measured in the gels depended on the cross-link

206 Some products had concentrations of menthol ("Menthol Arctic") and ethyl maltol ("No.

207 Menthol, menthone, pulegone and eucalyptol were identifi

208 ist-induced desensitization, suggesting that menthol must be present during the application of agonis

209 eviously reported, marked effects of chronic menthol on beta2* nAChRs studied in the same expression

210 tudies should explore the apparent effect of menthol on BNA in men.

211 the effect of low and high concentrations of menthol on corneal cool cells.

212 thysmography, we investigated the effects of menthol on the respiratory sensory irritation response i

213 and action potential frequencies induced by menthol or by current injections were also higher in PLC

214 When exposed to menthol or cold, TRPM8 behaves like many ligand-gated ch

215 o 25 degrees C and cooling compounds such as menthol or icilin.

216 ents used flavored e-cigarettes, with fruit, menthol or mint, and candy, desserts, or other sweets be

217 e, the participant smoked exclusively either menthol or non-menthol research cigarettes for approxima

218 gnificantly larger currents induced by cold, menthol or WS-12, a specific TRPM8 agonist, compared to

219 ctivated by chemical cooling agents (such as menthol) or when ambient temperatures drop below approxi

220 ace preference (CPP) assay, we observed that menthol plus nicotine produces greater reward-related be

221 Menthol plus nicotine upregulates nAChR number and funct

222 icient conversion of (S)-(-)-limonene to the menthol precursor trans-isopiperitenol.

223 Thus, chronic menthol produces a cell-type-selective upregulation of a

224 Taken together, these data indicate that menthol promotes desensitization of alpha3beta4 nAChRs b

225 erol/g dry weight mushroom was attained with menthol: pyruvic acid.

226 hannel--TRP melastatin 8 (TRPM8) or cold and menthol receptor 1 (CMR1)--is activated by chemical cool

227 amily, TRPM8, commonly known as the cold and menthol receptor is the major component of testosterone-

228 ponses in vivo are dependent on the cold and menthol receptor transient receptor potential melastatin

229 technique to study the human cold-sensitive menthol receptor transient receptor potential melastatin

230 tential (TRP) family, including the cold and menthol receptor TRPM8.

231 N- and C-terminal deletions on the cold and menthol receptor, TRPM8, expressed heterologously in Sf2

232 tential (TRP) ion channels, most notably the menthol receptor, TRPM8.

233 ole of TRPM8 as the evolutionarily conserved menthol receptor.

234 brain slices and cultured midbrain neurons, menthol reduced DA neuron firing frequency and altered D

235 , namely the ketoreductases (-)-menthone:(-)-menthol reductase and (-)-menthone:(+)-neomenthol reduct

236 used to acquire the former menthone:(-)-(3R)-menthol reductase directly from mRNA isolated from the o

237 The recombinant menthone:(-)-(3R)-menthol reductase has a deduced size of 34,070 D and con

238 hol cigarettes across all subjects; however, menthol relative to non-menthol cigarettes were associat

239 AITC (allyl isothiocyanate; mustard oil) and menthol represent two distinct types of ligands at the m

240 ant smoked exclusively either menthol or non-menthol research cigarettes for approximately 1 week pri

241 evoked by 1-oleolyl-2-acetyl-sn-glycerol and menthol, respectively.

242 jor role in desensitization of both cold and menthol responses.

243 ad drastically reduced cold responses and no menthol responses.

244 se in TRPM8 expression and the percentage of menthol-responsive cutaneous sensory neurons.

245 ht specific residues within TM5 critical for menthol responsiveness.

246 ard-related behavior may be mediated through menthol's ability to stabilize lower-sensitivity nAChRs

247 We examined menthol's effects on recombinant human alpha3beta4 nAChR

248 Menthol's effects were not specific to acrolein, as ment

249 Menthol's effects were reversed by a TRPM8 antagonist, A

250 urons demonstrated that the cooling compound menthol selectively activates a subset of Vglut3(lineage

251 ple of the molecular transducer for cold and menthol sensation.

252 itive behavioral changes, TRPM8 and/or other menthol-sensitive channels appear to underpin a much lar

253 d that camphor sensitizes a subpopulation of menthol-sensitive native cutaneous nociceptors in the mo

254 his study we characterized two subclasses of menthol-sensitive neurons from cultures of dissociated m

255 V) subunits, with Na(V)1.1 driving firing in menthol-sensitive neurons, whereas other small-diameter

256 The cold- and menthol-sensitive receptor TRPM8 (transient receptor pot

257 menthol has been cloned and named cold- and menthol-sensitive receptor-1 (CMR1) or transient recepto

258 tive Na(V)s drive action potential firing in menthol-sensitive sensory neurons and contribute to thei

259 stellation of ion channels expressed in each menthol-sensitive subclass.

260 ally mediated by inhibition of the cold- and menthol-sensitive transient receptor potential melastati

261 The cold- and menthol-sensitive transient receptor potential melastati

262 potential phase-plot analyses, which showed menthol-sensitive Vglut3(lineage) neurons to have more d

263 age-gated sodium channel (Na(V)) currents in menthol-sensitive Vglut3(lineage) neurons were resistant

264 nt readily entered into slow inactivation in menthol-sensitive Vglut3(lineage) neurons.

265 ssed TRPM8 receptors, that the percentage of menthol-sensitive/cold-sensitive/capsaicin-sensitive neu

266 The increase in cool and menthol sensitivity correlated with a significant increa

267 We identified determinants of menthol sensitivity in two regions: putative transmembra

268 Ongoing firing activity and menthol sensitivity were higher in CCSN terminals of inj

269 ld thermoreceptors, enhancing their cold and menthol sensitivity, inducing a rise in the ongoing firi

270 channel that serves as the primary cold and menthol sensor in humans.

271 ly, member 8 (TRPM8) is the primary cold and menthol sensor in humans.

272 Further, menthol slowed or prevented the recovery of nAChRs from

273 nced cross-over design, 10 menthol and 9 non-menthol smokers (10 females and 9 males; mean age 44.3)

274 nity-based cohort with the largest number of menthol smokers being traced.

275 kers of menthol cigarettes is lower than non-menthol smokers requires identifying the neurons that ar

276 l cigarettes indicates lower cancer risk for menthol smokers, but for cardiovascular disease (CVD) mo

277 Thus, menthol stabilizes lower-sensitivity alpha4* and alpha6

278 by destabilizing the closed channel, whereas menthol stabilizes the open channel, relative to the tra

279 Menthol stimulates olfactory sensations, and interacts w

280 that were also seen following capsaicin and menthol stimulation.

281 Menthol, the cooling agent in peppermint, is added to al

282 ld lead to improved production yields of (-)-menthol, the principal and characteristic flavor compone

283 From menthol to cholesterol to Taxol, terpenes are a ubiquito

284 how menthol activates the channel, we docked menthol to the channel and systematically validated our

285 Chronic menthol treatment accelerated desensitization of 100 and

286 Chronic menthol treatment at 500 nM, near the estimated menthol

287 Chronic menthol treatment failed to change the current density (

288 Four chemicals were present in 50% (menthol, triacetin, and cinnamaldehyde) to 80% (ethyl ma

289 Menthol (TRPM8-Y745H)- and icilin (TRPM8-N799A)-insensit

290 Capsaicin and menthol, two other topically applied agents widely used

291 Conversely, activating TRPM8 with menthol up-regulated UCP-1 expression and augmented unco

292 We observed that menthol uses its hydroxyl group as a hand to specificall

293 performed experiments on ethyl crotonate and menthol, using three different types of NMR chips aiming

294 Menthol was efficiently absorbed in the respiratory trac

295 ession, and mitigated uncoupled respiration; menthol was less capable of augmenting uncoupled respira

296 TRP channel agonists anandamide and (-)menthol were found to inhibit and activate RyR1, respect

297 A2) form of the enzyme, whereas responses to menthol were less sensitive to iPLA2 inhibition.

298 e show that human TRPA1 is only activated by menthol, whereas TRPA1 from nonmammalian species are ins

299 lones that are affected in their response to menthol while retaining channel function.

300 Coapplication of menthol with acetylcholine or nicotine increased desensi