(−)-menthol increases excitatory transmission by activating both TRPM8 and TRPA1 channels in mouse spinal lamina II layer

Luo, Yu‐Hui; Sun, Wuping; Feng, Xiao-Jin; Ba, Xiyuan; Liu, Tao; Guo, Jing; Xiao, Lizu; Jin, Jonghwa; Hao, Yue; Xiong, Dehua; Jiang, Changyu

doi:10.1016/j.bbrc.2019.06.135

Cited by 11 publications

(8 citation statements)

References 27 publications

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“…Wrigley et al (2009) previously reported that icilin, a TRPM8 and TRPA1 agonist, reduced the amplitude of primary afferent-evoked glutamatergic excitatory postsynaptic currents (EPSCs). In contrast, other reports showed that (−)-menthol, a TRPM8 and TRPA1 agonist, increased the miniature excitatory postsynaptic current frequency (Tsuzuki et al, 2004;Luo et al, 2019). These conflicting results about the effects of TRPM8 activation on excitatory neurons may be because of the difference in TRPM8 affinity and the effects of cooling compounds on TRPA1.…”

Section: Discussionmentioning

confidence: 84%

Suppressive Effects of Transient Receptor Potential Melastatin 8 Agonist on Epileptiform Discharges and Epileptic Seizures

et al. 2021

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Epilepsy is a relatively common condition, but more than 30% of patients have refractory epilepsy that is inadequately controlled by or is resistant to multiple drug treatments. Thus, new antiepileptic drugs based on newly identified mechanisms are required. A previous report revealed the suppressive effects of transient receptor potential melastatin 8 (TRPM8) activation on penicillin G-induced epileptiform discharges (EDs). However, it is unclear whether TRPM8 agonists suppress epileptic seizures or affect EDs or epileptic seizures in TRPM8 knockout (TRPM8KO) mice. We investigated the effects of TRPM8 agonist and lack of TRPM8 channels on EDs and epileptic seizures. Mice were injected with TRPM8 agonist 90 min after or 30 min before epilepsy-inducer injection, and electrocorticograms (ECoGs) were recorded under anesthesia, while behavior was monitored when awake. TRPM8 agonist suppressed EDs and epileptic seizures in wildtype (WT) mice, but not in TRPM8KO mice. In addition, TRPM8KO mice had a shorter firing latency of EDs, and EDs and epileptic seizures were deteriorated by the epilepsy inducer compared with those in WT mice, with the EDs being more easily propagated to the contralateral side. These findings suggest that TRPM8 activation in epileptic regions has anti-epileptic effects.

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Section: Discussionmentioning

confidence: 84%

Suppressive Effects of Transient Receptor Potential Melastatin 8 Agonist on Epileptiform Discharges and Epileptic Seizures

et al. 2021

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“…transmembrane conductance regulator (CFTR) channels and Na + -K + -2Cl À transporter, 50 5-HT 3 receptors, [51][52][53] Kv 7.2/3 channels, 54 TRP Ankyrin-1 (TRPA1) channels, 39,40,[55][56][57][58] and TRP vanilloid-3 (TRPV3) channels. 39,55,59 Because menthol is a highly hydrophobic and lipophilic compound with a lipid partition coefficient LogP value of 3.4, not only a nonspecific effect of menthol on the plasma membrane phospholipids but also specific binding of menthol to ion channel residues can modulate the functional properties of ion channels.…”

Section: Cystic Fibrosismentioning

confidence: 99%

“…Menthol, a cooling compound derived from mint leaves, is growing as an intriguing role in stimulating or inhibiting the activity of voltage-and ligand-gated ion channels. They include, but are not limited to, Ca 2+ channels, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] nicotinic acetylcholine receptors, [20][21][22][23][24][25][26][27][28] Na + channels, [29][30][31][32][33] transient receptor potential (TRP) melastatin-8 (TRPM8) channels, [34][35][36][37][38][39][40] γ-aminobutyric acid-type A (GABA A ) receptors, [41][42][43][44][45][46][47][48] Ca 2+ -activated K + channels,…”

Section: Introductionmentioning

confidence: 99%

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

Wang

2021

Chirality

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Both menthol and its analog WS-12 share the same hydrophobic intra-subunit binding pocket between a voltage-sensor-like domain and a TRP domain in a cold-sensing TRPM8 channel. However, unlike WS-12, menthol upregulates TRPM8 with a low efficacy but a high coefficient of a dose response at membrane hyperpolarization and with ligand stereoselectivity at membrane depolarization. The underlying mechanisms are unknown. Here, this in silico research suggested that the ligand-stereoselective sequential cooperativity between two menthol molecules in the WS-12 pocket is required for allosteric activation of TRPM8. Furthermore, two H-bonded homochiral menthol dimers with both head-to-head and head-to-tail can compete for the WS-12 site via non-covalent interactions. Although both dimers can form an H-bonding network with a voltage sensor S4 to disrupt a S3-S4 salt bridge in the voltage-sensor-like domain to release a "parking brake," only one dimer may drive channel opening by pushing a "gas pedal" in the TRP domain away from the S6 gate against S4. In this way, the efficacy is decreased, but the cooperativity is increased for the menthol effect at membrane hyperpolarization. Therefore, this review may extend a new pathway for ligand-stereoselective allosteric regulation of other voltage-and ligand-gated ion channels by menthol.

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“…In this system, the skin acts as a buffer between the body and the external environment and is dependent on the heat exchange between these areas. The temperature signal is transmitted via thermosensitive, cation-selective ion channels, the so-called instantaneous potential receptors (TRP): vanilloid receptors (TRPV1-4) [5], heat-activated and melastatin-activated (TRPM8), activated by low temperatures [6][7][8]. Researchers, including Noël et al [9] consider that other ionic channels also participate in low-temperature signal transmission: potassium channels with dual domains TRAAK and TREK1, which are activated by hyperpolarization and modulated by cyclic sodium and potassium nucleotides HCN1 channels [10].…”

Section: Basics Of Thermoregulationmentioning

confidence: 99%

Targeted temperature management: State of the Art

Szarpak

Smereka

Ruetzler

2019

Disaster Emerg Med J

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One of the indicated elements of post-resuscitation care is therapeutic hypothermia or temperature treatment management. the survivability of out-of-hospital cardiac arrest (OHCA) till admission to hospital is only 23%. Efficient thermoregulatory mechanisms are the basis for maintaining optimal body temperature. Therapeutic hypothermia shows normalizing effect on metabolic processes disturbed in ischaemic conditions, including improving metabolism and maintaining glucose balance in the brain, lowering the concentration of lactates, limiting the secretion of free radicals in damaged neurons, lowering the production of pro-inflammatory cytokines, stabilizes the blood-brain barrier and reduces endothelial dysfunction preventing ischaemic damage to tissues and organs. Hypothermia has a wide multidirectional effect on the human body, which can be useful in patients. Most available scientific studies show the efficacy and benefits of hypothermia in patients with out-of-hospital sudden cardiac arrest, including especially with ventricular fibrillation. The delay in the initiation of therapeutic hypothermia and reaching target temperature significantly increased the odds of a poor neurological outcome. Current American Heart Association (AHA) and European Resuscitation Council (ERC) resuscitation guidelines recommend that targeted temperature management should be implemented in all adult coma patients with return of spontaneous circulation (ROCS) after sudden cardiac arrest. The target temperature should be between 32°C and 36°C and then maintained for at least 24 hours. In patients with coma after TTM, fever should be actively prevented. For patients with out-of-hospital cardiac arrest, it is not recommended to routinely cool patients in prehospital conditions with a rapid intravenous infusion of cold fluids after ROSC.

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(−)-menthol increases excitatory transmission by activating both TRPM8 and TRPA1 channels in mouse spinal lamina II layer

Cited by 11 publications

References 27 publications

Suppressive Effects of Transient Receptor Potential Melastatin 8 Agonist on Epileptiform Discharges and Epileptic Seizures

Suppressive Effects of Transient Receptor Potential Melastatin 8 Agonist on Epileptiform Discharges and Epileptic Seizures

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

Targeted temperature management: State of the Art

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