TRPM8 Channels: Advances in Structural Studies and Pharmacological Modulation

Izquierdo, Carolina; Martín-Martínez, Mercedes; Gomez-Monterrey, Isabel; González-Muñiz, Rosario

doi:10.3390/ijms22168502

Cited by 19 publications

(15 citation statements)

References 165 publications

(216 reference statements)

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“…Its cytoplasmatic region comprises the C-terminal and D-terminal domains. The latter includes four melastatin zones [ 78 ]. The TRPA1 channel is another cold sensor.…”

Section: Structurementioning

confidence: 99%

Transient Receptor Potential (TRP) and Thermoregulation in Animals: Structural Biology and Neurophysiological Aspects

Lezama-García¹,

Mota-Rojas²,

Pereira³

et al. 2022

Animals

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This review presents and analyzes recent scientific findings on the structure, physiology, and neurotransmission mechanisms of transient receptor potential (TRP) and their function in the thermoregulation of mammals. The aim is to better understand the functionality of these receptors and their role in maintaining the temperature of animals, or those susceptible to thermal stress. The majority of peripheral receptors are TRP cation channels formed from transmembrane proteins that function as transductors through changes in the membrane potential. TRP are classified into seven families and two groups. The data gathered for this review include controversial aspects because we do not fully know the mechanisms that operate the opening and closing of the TRP gates. Deductions, however, suggest the intervention of mechanisms related to G protein-coupled receptors, dephosphorylation, and ligands. Several questions emerge from the review as well. For example, the future uses of these data for controlling thermoregulatory disorders and the invitation to researchers to conduct more extensive studies to broaden our understanding of these mechanisms and achieve substantial advances in controlling fever, hyperthermia, and hypothermia.

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“…Its cytoplasmatic region comprises the C-terminal and D-terminal domains. The latter includes four melastatin zones [ 78 ]. The TRPA1 channel is another cold sensor.…”

Section: Structurementioning

confidence: 99%

Transient Receptor Potential (TRP) and Thermoregulation in Animals: Structural Biology and Neurophysiological Aspects

Lezama-García¹,

Mota-Rojas²,

Pereira³

et al. 2022

Animals

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“…In addition, the expression of the same mSR in different but strictly connected tissues in the TME also offers the possibility to intervene not only on the tumorigenic process itself but also in cancer-sustaining mechanisms. Synthetic and natural compounds able to bind mSRs here presented-apart from TRPM8 and GPER, whose molecular modulators were recently and excellently reviewed [203,204]-are listed in Table 1. PaCa-2 cells (pancreatic cancer) RACK1, alpha-Actinin-1 Reduced PGRMC1 interactions with the actin cytoskeleton [225] Human granulosa/luteal cell B-cell lymphoma 2 (BCL2) pathway Increased PGRMC1 monomeric form, increased proapoptotic Harakiri (Hrk) expression [226] Due to the relative novelty of mSRs as mediators of steroid signaling, studies on mSRactive compounds here presented were limited to the pre-clinical phase.…”

Section: Msrs As Drug Targetsmentioning

confidence: 99%

Section: Beyond Msrs Physiologic Rolementioning

confidence: 99%

Molecular Characterization of Membrane Steroid Receptors in Hormone-Sensitive Cancers

Masi

Racchi

Travelli

et al. 2021

Cells

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Cancer is one of the most common causes of death worldwide, and its development is a result of the complex interaction of genetic factors, environmental cues, and aging. Hormone-sensitive cancers depend on the action of one or more hormones for their development and progression. Sex steroids and corticosteroids can regulate different physiological functions, including metabolism, growth, and proliferation, through their interaction with specific nuclear receptors, that can transcriptionally regulate target genes via their genomic actions. Therefore, interference with hormones’ activities, e.g., deregulation of their production and downstream pathways or the exposition to exogenous hormone-active substances such as endocrine-disrupting chemicals (EDCs), can affect the regulation of their correlated pathways and trigger the neoplastic transformation. Although nuclear receptors account for most hormone-related biologic effects and their slow genomic responses are well-studied, less-known membrane receptors are emerging for their ability to mediate steroid hormones effects through the activation of rapid non-genomic responses also involved in the development of hormone-sensitive cancers. This review aims to collect pre-clinical and clinical data on these extranuclear receptors not only to draw attention to their emerging role in cancer development and progression but also to highlight their dual role as tumor microenvironment players and potential candidate drug targets.

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“…According to a number of authors at present [ 1 , 2 , 3 , 4 , 5 ], thermosensitive ion channels, including the TRP (transient receptor potential) family of channels, are primary detectors of temperature changes in warm-blooded animals and are claimed to be the molecular basis of thermal sensitivity. Moreover, the ability of these channels to be activated by temperature changes and by nonthermal stimuli (chemical agonists) of natural and artificial origin makes these channels promising targets for medical treatments [ 2 , 3 , 6 , 7 , 8 ].…”

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

Khramova¹,

Evtushenko²,

Kozyreva³

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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TRPM8 Channels: Advances in Structural Studies and Pharmacological Modulation

Cited by 19 publications

References 165 publications

Transient Receptor Potential (TRP) and Thermoregulation in Animals: Structural Biology and Neurophysiological Aspects

Transient Receptor Potential (TRP) and Thermoregulation in Animals: Structural Biology and Neurophysiological Aspects

Molecular Characterization of Membrane Steroid Receptors in Hormone-Sensitive Cancers

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

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