ArticleBritish journal of pharmacology2013
Sphingosine and FTY720 are potent inhibitors of the transient receptor potential melastatin 7 (TRPM7) channels.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 122 citations in OpenAlex.
- Triple-Frequency Electromagnetic Stimulation Combined with Fingolimod Reduces Breast Cancer Cell Proliferation and Metastasis-Associated Extracellular Vesicle Protein Levels.Pharmaceuticals (Basel, Switzerland) · 2026Article
- TRPM7 in Peripheral and Central Immune Cells: Emerging Roles in Neuroinflammation and Neurological Disease.International journal of molecular sciences · 2026Review
- Calcium Signaling in Cardiac Fibroblasts: Roles in Fibrosis and Therapeutic Implications.Cardiovascular drugs and therapy · 2026Review
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- TRPM7 underlies cadmium cytotoxicity in pulmonary cells.Archives of toxicology · 2025Article
- CaBiomedicines · 2025Review
- The TRPM7 chanzyme in smooth muscle cells drives abdominal aortic aneurysm in mice.Nature cardiovascular research · 2025Article
- Article
- Endosomal fusion of pH-dependent enveloped viruses requires ion channel TRPM7.Nature communications · 2024Article
- Use of tetraethylammonium (TEA) and Tris loading for blocking TRPM7 channels in intact cells.Frontiers in pharmacology · 2024Article
- Analogs of FTY720 inhibit TRPM7 but not S1PRs and exert multimodal anti-inflammatory effects.The Journal of general physiology · 2024Article
- Ameliorative effects of Fingolimod (FTY720) on microglial activation and psychosis-related behavior in short term cuprizone exposed mice.Molecular brain · 2023Article
- Cardiac PDGFRαFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Gene-nutrient interactions that impact magnesium homeostasis increase risk for neural tube defects in mice exposed to dolutegravir.Frontiers in cell and developmental biology · 2023Article
- Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology.Frontiers in physiology · 2023Review
- Cell death induction and protection by activation of ubiquitously expressed anion/cation channels. Part 3: the roles and properties of TRPM2 and TRPM7.Frontiers in cell and developmental biology · 2023Review
- Efferocytosis requires periphagosomal CaNature communications · 2022Article
- Potential of the TRPM7 channel as a novel therapeutic target for pulmonary arterial hypertension.Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2022Review
- Molecular Pharmacology and Novel Potential Therapeutic Applications of Fingolimod.Frontiers in pharmacology · 2022Review
- Substantial involvement of TRPM7 inhibition in the therapeutic effect of Ophiocordyceps sinensis on pulmonary hypertension.Translational research : the journal of laboratory and clinical medicine · 2021Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
background and purposeTransient receptor potential melastatin 7 (TRPM7) is a unique channel kinase which is crucial for various physiological functions. However, the mechanism by which TRPM7 is gated and modulated is not fully understood. To better understand how modulation of TRPM7 may impact biological processes, we investigated if TRPM7 can be regulated by the phospholipids sphingosine (SPH) and sphingosine-1-phosphate (S1P), two potent bioactive sphingolipids that mediate a variety of physiological functions. Moreover, we also tested the effects of the structural analogues of SPH, N,N-dimethyl-D-erythro-sphingosine (DMS), ceramides and FTY720 on TRPM7. EXPERIMENTAL APPROACH: HEK293 cells stably expressing TRPM7 were used for whole-cell, single-channel and macropatch current recordings. Cardiac fibroblasts were used for native TRPM7 current recording. KEY
resultsSPH potently inhibited TRPM7 in a concentration-dependent manner, whereas S1P and other ceramides did not produce noticeable effects. DMS also markedly inhibited TRPM7. Moreover, FTY720, an immunosuppressant and the first oral drug for treatment of multiple sclerosis, inhibited TRPM7 with a similar potency to that of SPH. In contrast, FTY720-P has no effect on TRPM7. It appears that SPH and FTY720 inhibit TRPM7 by reducing channel open probability. Furthermore, endogenous TRPM7 in cardiac fibroblasts was markedly inhibited by SPH, DMS and FTY720. CONCLUSIONS AND IMPLICATIONS: This is the first study demonstrating that SPH and FTY720 are potent inhibitors of TRPM7. Our results not only provide a new modulation mechanism of TRPM7, but also suggest that TRPM7 may serve as a direct target of SPH and FTY720, thereby mediating S1P-independent physiological/pathological functions of SPH and FTY720.
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