Effects of Activation of TRPM8 Ion Channels on Thermoregulatory Reactions in Cooling

Козырева, Т. В.; Kozaruk, V. P.; Tkachenko, E. Ya.; Khramova, G. M.

doi:10.1007/s11055-012-9617-8

Cited by 4 publications

(6 citation statements)

References 24 publications

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“…It is known, that a cold exposure stimulates fat metabolism, resulting in a decrease of a respiratory coefficient [33]. The activation of TRPM8 channels by menthol in thermoneutral conditions also reduces the respiratory coefficient [34]. It is also known that the patients with arterial hypertension show a characteristically altered pattern of plasma lipids [35] These changes are associated with high risk of development of arteriosclerosis and cardiovascular diseases.…”

Section: Discussionmentioning

confidence: 99%

Inherited stress-induced hypertension associates with altered gene expression of thermosensitive TRP ion channels in hypothalamus

Voronova¹,

Tuzhikova²,

Markel³

et al. 2015

J Exp Integr Med

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Objective: The widespread essential hypertension, of which the nature is still unclear, demands a comprehensive study of the differences between normo-and hypertensives. Hypertension may be associated with changes in the central nervous system functioning, at various levels. Our previous data have shown the differences in thermo-responsiveness of normotensive and hypertensive rats. Thermosensitive TRP (transient receptor potential) ion channels which are considered as a molecular basis of the thermosensitivity are essential for thermoregulation. Hypothalamus is the important brain structure for blood pressure and temperature regulation. The aim of present work was to assess the expression of thermosensitive TRP ion channel genes in functionally different parts of hypothalamus in normo-and hypertensive rats. Methods: Male inherited stress-induced arterial hypertensive (ISIAH) rats and normotensive Wistar Albino Glaxo (WAG) were used. Gene expression was assayed by the quantitative method of reverse transcription-polymerase-chain-reaction (RT-PCR). Results: Differences between normal and hypertensive rats were found in the expression of transient receptor potential melastatin 8 (Trpm8) and transient receptor potential vanilloid 4 (Trpv4) genes. The level of Trpm8 mRNA in the anterior hypothalamus of hypertensives was more than twice lower than in normotensives. In hypertensives, the level of Trpv4 mRNA in posterior hypothalamus was half time higher than in anterior, and significantly higher than in the normotensives. In normotensives, the Trpv4 gene expression was the same in both parts of hypothalamus. Some differences between anterior and posterior hypothalamus were similar in normo-and hypertensives: the level of Trpm8 mRNA in the anterior hypothalamus was three times higher than in the posterior and the levels of Trpv1 and transient receptor potential ankyrin 1 (Trpa1) mRNA, vice versa. Conclusion: The obtained data allow to come closer to understand the possible molecular bases of the status of hypertension and elucidate some aspects of the physiological role of the investigated thermosensitive TRP ion channels.

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Section: Discussionmentioning

confidence: 99%

Inherited stress-induced hypertension associates with altered gene expression of thermosensitive TRP ion channels in hypothalamus

Voronova¹,

Tuzhikova²,

Markel³

et al. 2015

J Exp Integr Med

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“…Our preactivation of the TRPM8 peripheral ion channel with menthol in hypertensive rats did not affect their thermoregulatory responses in the present study. This is their significant difference from normotensive animals, which have been characterized elsewhere [ 16 , 17 ]. It is shown that, in normotensive animals, the application of menthol to the skin, even under thermoneutral conditions, raises oxygen consumption and diminishes the respiratory exchange ratio, whereas upon cooling, the menthol application shortens the latency periods of thermoregulatory reactions and lowers the temperature thresholds at which the reactions are triggered [ 16 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…These data indicate that nonthermal activation of TRPM8 even under thermoneutral conditions causes the same physiological responses in warm-blooded animals as does cold exposure: acceleration of overall metabolism and greater use of lipids as an oxidation substrate [ 14 , 15 ]. Pharmacological preactivation of the peripheral TRPM8 also influences the development of thermoregulatory responses of the organism to subsequent cooling, by decreasing the thresholds of all thermoregulatory reactions without changing the sequence of their initiation [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of Skin Ion Channel TRPM8 Activation by Cold and Menthol on Thermoregulation and the Expression of Genes of Thermosensitive TRP Ion Channels in the Hypothalamus of Hypertensive Rats

Voronova

Khramova

Evtushenko

et al. 2022

IJMS

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ISIAH (inherited stress-induced arterial hypertension) rats are characterized by high blood pressure and decreased Trpm8 gene expression in the anterior hypothalamus. Thermosensitive ion channel TRPM8 plays a critical role in the transduction of moderately cold stimuli that give rise to cool sensations. In normotensive animals, the activation of skin TRPM8 is known to induce changes in gene expression in the hypothalamus and induce alterations of thermoregulatory responses. In this work, in hypertensive rats, we studied the effects of activation of the peripheral TRPM8 by cooling and by application of a 1% menthol suspension on (1) the maintenance of body temperature balance and (2) mRNA expression of thermosensitive TRP ion channels in the hypothalamus. In these hypertensive animals, (1) pharmacological activation of peripheral TRPM8 did not affect the thermoregulatory parameters either under thermoneutral conditions or during cold exposure; (2) the expression of Trpm8 in the anterior hypothalamus approximately doubled (to the level of normotensive animals) under the influence of (a) slow cooling and (b) at pharmacological activation of the peripheral TRPM8 ion channel. The latter fact seems the quite important because it allows the proposal of a tool for correcting at least some parameters that distinguish a hypertensive state from the normotensive one.

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“…55 Even in thermoneutral conditions, TRPM8 activation by topical menthol application increased oxygen consumption and decreased the respiratory coefficient, suggesting that TRPM8 activation may promote fat oxidation. 45 TRPM8 agonism with intragastric menthol or 1,8-cineole increased thermogenesis in mice. 41 Topical menthol increased core body temperature, shivering, oxygen consumption, tail skin vasoconstriction, and heatseeking behavior in mice.…”

Section: Trpm8 Channels In Energy Homeostasismentioning

confidence: 92%

Menthol to Induce Non-shivering Thermogenesis via TRPM8/PKA Signaling for Treatment of Obesity

Sanders

Rajagopal

Rajagopal³

2021

Journal of Obesity & Metabolic Syndrome

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Increasing basal energy expenditure via uncoupling protein 1 (UCP1)-dependent non-shivering thermogenesis is an attractive therapeutic strategy for treatment of obesity. Transient receptor potential melastatin 8 (TRPM8) channel activation by cold and cold mimetics induces UCP1 transcription and prevents obesity in animals, but the clinical relevance of this relationship remains incompletely understood. A review of TRPM8 channel agonism for treatment of obesity focusing on menthol was undertaken. Adipocyte TRPM8 activation results in Ca 2+ influx and protein kinase A (PKA) activation, which induces mitochondrial elongation, mitochondrial localization to lipid droplets, lipolysis, β-oxidation, and UCP1 expression. Ca 2+ -induced mitochondrial reactive oxygen species activate UCP1. In animals, TRPM8 agonism increases basal metabolic rate, non-shivering thermogenesis, oxygen consumption, exercise endurance, and fatty acid oxidation and decreases abdominal fat percentage. Menthol prevents high-fat diet-induced obesity, glucose intolerance, insulin resistance, and liver triacylglycerol accumulation. Hypothalamic TRPM8 activation releases glucagon, which activates PKA and promotes catabolism. TRPM8 polymorphisms are associated with obesity. In humans, oral menthol and other TRPM8 agonists have little effect. However, topical menthol appears to increase core body temperature and metabolic rate. A randomized clinical control trial of topical menthol in obese patients is warranted.

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Effects of Activation of TRPM8 Ion Channels on Thermoregulatory Reactions in Cooling

Cited by 4 publications

References 24 publications

Inherited stress-induced hypertension associates with altered gene expression of thermosensitive TRP ion channels in hypothalamus

Inherited stress-induced hypertension associates with altered gene expression of thermosensitive TRP ion channels in hypothalamus

Effect of Skin Ion Channel TRPM8 Activation by Cold and Menthol on Thermoregulation and the Expression of Genes of Thermosensitive TRP Ion Channels in the Hypothalamus of Hypertensive Rats

Menthol to Induce Non-shivering Thermogenesis via TRPM8/PKA Signaling for Treatment of Obesity

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