Ask about this productRelated genes to: TRPM8 Blocking Peptide
- Gene:
- TRPM8 NIH gene
- Name:
- transient receptor potential cation channel subfamily M member 8
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 2q37.1
- Locus Type:
- gene with protein product
- Date approved:
- 2002-01-11
- Date modifiied:
- 2016-10-05
Related products to: TRPM8 Blocking Peptide
Related articles to: TRPM8 Blocking Peptide
- Insomnia is a common sleep disorder frequently comorbid with anxiety and is often attributed to psychophysiological hyperarousal. While internal and behavioral factors are typically emphasized, environmental sensory exposures are less commonly recognized as potential contributors to sleep disturbance. Menthol, a widely used compound in oral hygiene products, activates transient receptor potential melastatin 8 (TRPM8) receptors, which are known to influence acute sensory and arousal responses. However, their role in chronic sleep disturbance remains unclear. - Source: PubMed
Publication date: 2026/04/27
Alateeq Fahad A - Chronic pain following nerve injury (neuropathic pain), is notoriously difficult to treat, with current analgesics showing limited efficacy and adverse or dangerous side effects. One new candidate analgesic target is the TRPM8 ion channel, identified as the peripheral detector for innocuous cool sensation and reported to attenuate spinal cord pain processing by processes involving inhibitory metabotropic glutamate (mGlu) receptors. - Source: PubMed
Publication date: 2026/04/14
Mitchell RorySun LitingCzapranska MartaFleetwood-Walker Sue - Pulmonary arterial hypertension (PAH) remains a fatal condition with limited treatment options. While phosphodiesterase-5 (PDE5) inhibitors such as sildenafil and tadalafil are standard treatments, their therapeutic efficacy is limited by poor aqueous solubility and an incomplete understanding of the mechanisms underlying their long-term benefits on vascular remodeling. To overcome these critical limitations, we developed a novel, highly water-soluble potassium salt polymorph of a PDE5 inhibitor, designated CPD1. In a monocrotaline-induced rat model of PAH, CPD1 demonstrated superior in vivo efficacy. It dose-dependently alleviated key pathological hallmarks by significantly reducing pulmonary arterial pressure, reversing right ventricular hypertrophy, and inhibiting the remodeling of small muscular pulmonary arteries. At the vascular level, CPD1 significantly attenuated the enhanced contractile responses to endothelin-1, cyclopiazonic acid, and 1-oleoyl-2-acetyl-sn-glycerol in endothelium-denuded arteries. Mechanistically, we reveal a novel dual-pathway mechanism: in addition to elevating cyclic guanosine monophosphate (cGMP) through PDE5 inhibition, CPD1 uniquely and dose-dependently upregulates the expression of the transient receptor potential melastatin-8 (TRPM8) channel. This upregulation sensitizes the pulmonary vasculature, markedly enhancing vasodilation induced by TRPM8 activation. Our findings position CPD1 not merely as a more soluble PDE5 inhibitor but as a first-in-class agent that simultaneously modulates the cGMP pathway and the TRPM8 channel, offering a promising new therapeutic strategy to correct dysregulated calcium homeostasis and reverse vascular remodeling in PAH. - Source: PubMed
Publication date: 2026/04/22
Mu YunpingSun JinlinZhang XindanZhu HuidanLi BinQiu HaohengZhao ZhenggangZhou SujinLi FanghongZhao Allan Zijian - Cooling agents (chemicals added to impart a cooling sensation) in tobacco products are receiving increased attention due to their use as menthol substitutes. However, detailed information on their chemical structures, physico-chemical properties, cooling activity, and human and ecotoxicity potential has not been compiled. Our goal was to profile cooling agents that could be used as menthol substitutes in tobacco products, along with descriptions of their cooling properties and estimated toxicological effects. First, we compiled a library of 228 cooling agents, including 180 unique two-dimensional (2-D) chemical structures based on a review of multiple public data sources (literature, invention patents, and public databases). The library includes chemicals with a "cool" and/or "mint" flavor profile as designated by the Flavor and Extract Manufacturers Association (FEMA), chemicals reported to activate the cation channel transient receptor potential melastatin 8 (TRPM8) receptor, and/or chemicals with reported subjective perceived sensory cooling. Second, we classified the cooling agents into three main chemical skeletons using similar structural motifs and estimated their physico-chemical properties related to cooling attributes using Schrödinger Canvas software, including log octanol-water partition coefficient (LogKow), vapor pressure, and electrotopological state index. Third, to investigate the cooling agents' similarity to each other and to menthol, we applied an unsupervised machine learning algorithm (Knowledge Discovery by Accuracy Maximization [KODAMA]) and hierarchical clustering techniques and identified six clusters. Fourth, we compiled available perceived cooling intensity data. Fifth, we used models based on experimental and predicted data (EPA's web-based Hazard Comparison Module [HCM]) to estimate human health toxicity and ecotoxicity. Some cooling agents are associated with genotoxicity, developmental toxicity, skin irritation, and eye irritation, and pose toxicity to fish, algae, and invertebrates. Using this surveillance approach will help inform future tobacco regulatory decisions and policies by profiling chemicals used as cooling agents in tobacco products and those that pose potential health hazard concerns. - Source: PubMed
Publication date: 2026/04/16
Chakraborty SaibalVenugopal P DilipKaltcheva MariaKang Jueichuan ConnieGoel Reema - The prolonged interaction between the immune system and tumor antigens can result in T cell exhaustion. Extensive research has been conducted on strategies to reactivate exhausted T cells within the tumor microenvironment. However the exact contribution of the endocannabinoid system (ECS) and nociceptors in regulating CD8+ T cells within the framework of cancer-related inflammation has not been thoroughly studied. This study investigated the use of a TRPM8 antagonist (RQ-00203078), a selective cannabinoid receptor 1 (CB1) antagonist (AM251), and alpelisib (BYL-719) to control CD8+ T cell exhaustion. Our findings showed that administration of the CB1 antagonist AM251, either alone or in combination with alpelisib, significantly reduced the expression of PD-1 and Lag-3 on CD8+ T cells. Interestingly, treatment with the TRPM8 antagonist led to a notable increase in PD-1 expression on CD8+ T cells. These findings suggest that the decreased expression of inhibitory receptors on CD8+ T cells after treatment with the CB1 antagonist whether alone or with alpelisib and TRPM8 highlights the potential of ECS as a promising therapeutic target in cancer treatment. - Source: PubMed
Publication date: 2026/04/10
Mohammadzadeh AdelMoazzendizzaji SahandMohammadi Aliasghar TabatabaeiAhmadi AfsanehMahmodlou RahimPourfathollah Ali Akbar