Transient receptor potential channels as therapeutic targets (original) (raw)

• Patapoutian, A., Tate, S. & Woolf, C. J. Transient receptor potential channels: targeting pain at the source. Nature Rev. Drug Discov. 8, 55–68 (2009).
  Article CAS Google Scholar
• Szallasi, A., Cortright, D. N., Blum, C. A. & Eid, S. R. The vanilloid receptor TRPV1, 10 years from channel cloning to antagonist proof-of-concept. Nature Rev. Drug Discov. 6, 357–372 (2007).
  Article CAS Google Scholar
• Wu, L. J., Sweet, T. B. & Clapham, D. E. International Union of Basic and Clinical Pharmacology. LXXVI. Current progress in the mammalian TRP ion channel family. Pharmacol. Rev. 62, 381–404 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Nilius, B. & Owsianik, G. Transient receptor potential channelopathies. Pflugers Arch. 460, 437–450 (2010).
  Article CAS PubMed Google Scholar
• Szallasi, A. & Blumberg, P. M. Vanilloid (capsaicin) receptors and mechanisms. Pharmacol. Rev. 51, 159–212 (1999).
  CAS PubMed Google Scholar
• Fanger, C. M., del Camino, D. & Moran, M. M. TRPA1 as an analgesic target. Open Drug Discov. J. 2, 63–69 (2010).
  Article CAS Google Scholar
• McKemy, D. D. Therapeutic potential of TRPM8 modulators. Open Drug Discov. J. 2, 80–87 (2010).
  Article CAS Google Scholar
• Everaerts, W., Nilius, B. & Owsianik, G. The vanilloid transient receptor potential channel TRPV4: from structure to disease. Prog. Biophys. Mol. Biol. 103, 2–17 (2010).
  Article CAS PubMed Google Scholar
• Caterina, M. J. et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389, 816–824 (1997).
  Article CAS PubMed Google Scholar
• Gavva, N. R. et al. Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans. Pain 136, 202–210 (2008).
  Article CAS PubMed Google Scholar
• Iida, T., Shimizu, I., Nealen, M. L., Campbell, A. & Caterina, M. Attenuated fever response in mice lacking TRPV1. Neurosci. Lett. 378, 28–33 (2005).
  Article CAS PubMed Google Scholar
• Toth, D. M. et al. Nociception, neurogenic inflammation and thermoregulation in TRPV1 knockdown transgenic mice. Cell. Mol. Life Sci. 11 Nov 2010 (doi:10.1007/s00018-010-0569-2).
• Garami, A. et al. Thermoregulatory phenotype of the Trpv1 knockout mouse: thermoeffector dysbalance with hyperkinesis. J. Neurosci. 31, 1721–1733 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Romanovsky, A. A. et al. The transient receptor potential vanilloid-1 channel in thermoregulation: a thermosensor it is not. Pharmacol. Rev. 61, 228–261 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Gavva, N. R. et al. Repeated administration of vanilloid receptor TRPV1 antagonists attenuates hyperthermia elicited by TRPV1 blockade. J. Pharmacol. Exp. Ther. 323, 128–137 (2007).
  Article CAS PubMed Google Scholar
• Rowbotham, M. C. et al. Oral and cutaneous thermosensory profile of selective TRPV1 inhibition by ABT-102 in a randomized healthy volunteer trial. Pain 152, 1192–1200 (2011).
  Article CAS PubMed Google Scholar
• Krarup, A. L. et al. Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain. Aliment. Pharmacol. Ther. 33, 1113–1122 (2011). This was the first report of a TRPV1 antagonist that had clinical efficacy in a painful disease state without causing significant adverse effects.
  Article CAS PubMed Google Scholar
• Lehto, S. G. et al. Antihyperalgesic effects of (R,E)-_N_-(2-hydroxy-2, 3-dihydro-1_H_-inden-4-yl)-3-(2-(piperidin-1-yl)-4-(tri fluoromethyl)phenyl)-acrylamide (AMG8562), a novel transient receptor potential vanilloid type 1 modulator that does not cause hyperthermia in rats. J. Pharmacol. Exp. Ther. 326, 218–229 (2008).
  Article CAS PubMed Google Scholar
• Chizh, B. A. et al. The effects of the TRPV1 antagonist SB-705498 on TRPV1 receptor-mediated activity and inflammatory hyperalgesia in humans. Pain 132, 132–141 (2007).
  Article CAS PubMed Google Scholar
• Knotkova, H., Pappagallo, M. & Szallasi, A. Capsaicin (TRPV1 agonist) therapy for pain relief: farewell or revival? Clin. J. Pain 24, 142–154 (2008).
  Article PubMed Google Scholar
• Noto, C., Pappagallo, M. & Szallasi, A. NGX-4010, a high-concentration capsaicin dermal patch for lasting relief of peripheral neuropathic pain. Curr. Opin. Investig. Drugs 10, 702–710 (2009).
  CAS PubMed Google Scholar
• Li, H., Wang, S., Chuang, A. Y., Cohen, B. E. & Chuang, H. H. Activity-dependent targeting of TRPV1 with a pore-permeating capsaicin analog. Proc. Natl Acad. Sci. USA 108, 8497–8502 (2011).
  Article PubMed PubMed Central Google Scholar
• Story, G. M. et al. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112, 819–829 (2003).
  Article CAS PubMed Google Scholar
• Bautista, D. M. et al. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 124, 1269–1282 (2006).
  Article CAS PubMed Google Scholar
• Bessac, B. F. et al. TRPA1 is a major oxidant sensor in murine airway sensory neurons. J. Clin. Invest. 118, 1899–1910 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Satoh, J. & Yamakage, M. Desflurane induces airway contraction mainly by activating transient receptor potential A1 of sensory C-fibers. J. Anesth. 23, 620–623 (2009).
  Article PubMed Google Scholar
• Bessac, B. F. et al. Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases. FASEB J. 23, 1102–1114 (2009). This was the first demonstration that activation of TRPA1 is both necessary and sufficient to cause nocifensive reflexes in response to inhalation of a broadly reactive respiratory irritant.
  Article CAS PubMed PubMed Central Google Scholar
• Taylor-Clark, T. E., Kiros, F., Carr, M. J. & McAlexander, M. A. Transient receptor potential ankyrin 1 mediates toluene diisocyanate-evoked respiratory irritation. Am. J. Respir. Cell Mol. Biol. 40, 756–762 (2009).
  Article CAS PubMed Google Scholar
• Taylor-Clark, T. E. & Undem, B. J. Ozone activates airway nerves via the selective stimulation of TRPA1 ion channels. J. Physiol. 588, 423–433 (2010).
  Article CAS PubMed Google Scholar
• Cruz-Orengo, L. et al. Cutaneous nociception evoked by 15-δ PGJ2 via activation of ion channel TRPA1. Mol. Pain 4, 30 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Trevisani, M. et al. 4-hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1. Proc. Natl Acad. Sci. USA 104, 13519–13524 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Kwan, K. Y. et al. TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron 50, 277–289 (2006).
  Article CAS PubMed Google Scholar
• McNamara, C. R. et al. TRPA1 mediates formalin-induced pain. Proc. Natl Acad. Sci. USA 104, 13525–13530 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Petrus, M. et al. A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition. Mol. Pain 3, 40 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Eid, S. R. et al. HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity. Mol. Pain 4, 48 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Wei, H., Hamalainen, M. M., Saarnilehto, M., Koivisto, A. & Pertovaara, A. Attenuation of mechanical hypersensitivity by an antagonist of the TRPA1 ion channel in diabetic animals. Anesthesiology 111, 147–154 (2009).
  Article CAS PubMed Google Scholar
• Katsura, H. et al. Antisense knock down of TRPA1, but not TRPM8, alleviates cold hyperalgesia after spinal nerve ligation in rats. Exp. Neurol. 200, 112–123 (2006).
  Article CAS PubMed Google Scholar
• del Camino, D. et al. TRPA1 contributes to cold hypersensitivity. J. Neurosci. 30, 15165–15174 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• da Costa, D. S. et al. The involvement of the transient receptor potential A1 (TRPA1) in the maintenance of mechanical and cold hyperalgesia in persistent inflammation. Pain 148, 431–437 (2010).
  Article CAS PubMed Google Scholar
• Chen, J. et al. Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation. Pain 152, 1165–1172 (2011).
  Article CAS PubMed Google Scholar
• McGaraughty, S. et al. TRPA1 modulation of spontaneous and mechanically evoked firing of spinal neurons in uninjured, osteoarthritic, and inflamed rats. Mol. Pain 6, 14 (2010). This was the first demonstration that a TRPA1 antagonist is capable of relieving pathological pain in animal models without altering cold sensation in naive animals.
  Article CAS PubMed PubMed Central Google Scholar
• Kerstein, P. C., del Camino, D., Moran, M. M. & Stucky, C. L. Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptors. Mol. Pain 5, 19 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Kremeyer, B. et al. A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome. Neuron 66, 671–680 (2010). This paper was the first to link the activity of a TRP channel to a pain syndrome in humans. It also suggested that potentiation of TRPA1 by cold temperatures is physiologically relevant, as cold is one of the triggers for pain episodes in patients suffering from pain syndromes.
  Article CAS PubMed PubMed Central Google Scholar
• Cheng, X. et al. TRP channel regulates EGFR signaling in hair morphogenesis and skin barrier formation. Cell 141, 331–343 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Xu, H., Delling, M., Jun, J. C. & Clapham, D. E. Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels. Nature Neurosci. 9, 628–635 (2006).
  Article CAS PubMed Google Scholar
• Gopinath, P. et al. Increased capsaicin receptor TRPV1 in skin nerve fibres and related vanilloid receptors TRPV3 and TRPV4 in keratinocytes in human breast pain. BMC Womens Health 5, 2 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Facer, P. et al. Differential expression of the capsaicin receptor TRPV1 and related novel receptors TRPV3, TRPV4 and TRPM8 in normal human tissues and changes in traumatic and diabetic neuropathy. BMC Neurol. 7, 11 (2007). This was the first report of disease-related changes in the expression of TRPV1, TRPV3 and TRPV4 in painful disease states in humans.
  Article CAS PubMed PubMed Central Google Scholar
• Xiao, R. et al. Calcium plays a central role in the sensitization of TRPV3 channel to repetitive stimulations. J. Biol. Chem. 283, 6162–6174 (2008).
  Article CAS PubMed Google Scholar
• Khairatkar Joshi, N., Maharaj, N. & Thomas, A. The TRPV3 receptor as a pain target: a therapeutic promise or just some more new biology? Open Drug Discov. J. 2, 88–95 (2010).
  Google Scholar
• Moqrich, A. et al. Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin. Science 307, 1468–1472 (2005).
  Article CAS PubMed Google Scholar
• Okazawa, M. et al. Noxious heat receptors present in cold-sensory cells in rats. Neurosci. Lett. 359, 33–36 (2004).
  Article CAS PubMed Google Scholar
• Dhaka, A. et al. TRPM8 is required for cold sensation in mice. Neuron 54, 371–378 (2007).
  Article CAS PubMed Google Scholar
• Bautista, D. M. et al. The menthol receptor TRPM8 is the principal detector of environmental cold. Nature 448, 204–208 (2007).
  Article CAS PubMed Google Scholar
• Colburn, R. W. et al. Attenuated cold sensitivity in TRPM8 null mice. Neuron 54, 379–386 (2007).
  Article CAS PubMed Google Scholar
• Proudfoot, C. J. et al. Analgesia mediated by the TRPM8 cold receptor in chronic neuropathic pain. Curr. Biol. 16, 1591–1605 (2006).
  Article CAS PubMed Google Scholar
• Parks, D. J. et al. Design and optimization of benzimidazole-containing transient receptor potential melastatin 8 (TRPM8) antagonists. J. Med. Chem. 54, 233–247 (2011).
  Article CAS PubMed Google Scholar
• Andersson, K. E., Gratzke, C. & Hedlund, P. The role of the transient receptor potential (TRP) superfamily of cation-selective channels in the management of the overactive bladder. BJU Int. 106, 1114–1127 (2010).
  Article CAS PubMed Google Scholar
• Avelino, A. & Cruz, F. TRPV1 (vanilloid receptor) in the urinary tract: expression, function and clinical applications. Naunyn Schmiedebergs Arch. Pharmacol. 373, 287–299 (2006).
  Article CAS PubMed Google Scholar
• Everaerts, W. et al. Functional characterization of transient receptor potential channels in mouse urothelial cells. Am. J. Physiol. Renal Physiol. 298, F692–F701 (2010).
  Article CAS PubMed Google Scholar
• Birder, L. A. et al. Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nature Neurosci. 5, 856–860 (2002).
  Article CAS PubMed Google Scholar
• MacDonald, R., Monga, M., Fink, H. A. & Wilt, T. J. Neurotoxin treatments for urinary incontinence in subjects with spinal cord injury or multiple sclerosis: a systematic review of effectiveness and adverse effects. J. Spinal Cord Med. 31, 157–165 (2008).
  Article PubMed PubMed Central Google Scholar
• Cruz, C. D. et al. Intrathecal delivery of resiniferatoxin (RTX) reduces detrusor overactivity and spinal expression of TRPV1 in spinal cord injured animals. Exp. Neurol. 214, 301–308 (2008).
  Article CAS PubMed Google Scholar
• Cruz, F. & Dinis, P. Resiniferatoxin and botulinum toxin type A for treatment of lower urinary tract symptoms. Neurourol. Urodyn. 26, 920–927 (2007).
  Article CAS PubMed Google Scholar
• Sculptoreanu, A., de Groat, W. C., Buffington, C. A. & Birder, L. A. Protein kinase C contributes to abnormal capsaicin responses in DRG neurons from cats with feline interstitial cystitis. Neurosci. Lett. 381, 42–46 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Charrua, A. et al. GRC-6211, a new oral specific TRPV1 antagonist, decreases bladder overactivity and noxious bladder input in cystitis animal models. J. Urol. 181, 379–386 (2009).
  Article CAS PubMed Google Scholar
• Gevaert, T. et al. Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding. J. Clin. Invest. 117, 3453–3462 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Everaerts, W. et al. Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis. Proc. Natl Acad. Sci. USA 107, 19084–19089 (2010).
  Article PubMed PubMed Central Google Scholar
• Mochizuki, T. et al. The TRPV4 cation channel mediates stretch-evoked Ca2+ influx and ATP release in primary urothelial cell cultures. J. Biol. Chem. 284, 21257–21264 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Thorneloe, K. S. et al. N_-((1_S)-1-{[4-((2_S_)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl} -3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: part I. J. Pharmacol. Exp. Ther. 326, 432–442 (2008).
  Article CAS PubMed Google Scholar
• Mukerji, G. et al. Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations. BMC Urol. 6, 6 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Lashinger, E. S. et al. AMTB, a TRPM8 channel blocker: evidence in rats for activity in overactive bladder and painful bladder syndrome. Am. J. Physiol. Renal Physiol. 295, F803–F810 (2008).
  Article CAS PubMed Google Scholar
• Paus, R., Schmelz, M., Biro, T. & Steinhoff, M. Frontiers in pruritus research: scratching the brain for more effective itch therapy. J. Clin. Invest. 116, 1174–1186 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Biro, T. et al. TRP channels as novel players in the pathogenesis and therapy of itch. Biochim. Biophys. Acta 1772, 1004–1021 (2007).
  Article CAS PubMed Google Scholar
• Bodo, E. et al. Vanilloid receptor-1 (VR1) is widely expressed on various epithelial and mesenchymal cell types of human skin. J. Invest. Dermatol. 123, 410–413 (2004).
  Article CAS PubMed Google Scholar
• Stander, S. et al. Expression of vanilloid receptor subtype 1 in cutaneous sensory nerve fibers, mast cells, and epithelial cells of appendage structures. Exp. Dermatol. 13, 129–139 (2004).
  Article PubMed Google Scholar
• Shim, W. S. et al. TRPV1 mediates histamine-induced itching via the activation of phospholipase A2 and 12-lipoxygenase. J. Neurosci. 27, 2331–2337 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Weisshaar, E., Heyer, G., Forster, C. & Handwerker, H. O. Effect of topical capsaicin on the cutaneous reactions and itching to histamine in atopic eczema compared to healthy skin. Arch. Dermatol. Res. 290, 306–311 (1998).
  Article CAS PubMed Google Scholar
• Alenmyr, L., Hogestatt, E. D., Zygmunt, P. M. & Greiff, L. TRPV1-mediated itch in seasonal allergic rhinitis. Allergy 64, 807–810 (2009).
  Article CAS PubMed Google Scholar
• Wilson, S. R. et al. TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor-mediated itch. Nature Neurosci. 14, 595–602 (2011). This study showed that TRPA1 not only mediates pain and airway irritation but is also required for histamine-independent itch.
  Article CAS PubMed Google Scholar
• Carrillo, P. et al. Cutaneous wounds produced by capsaicin treatment of newborn rats are due to trophic disturbances. Neurotoxicol. Teratol. 20, 75–81 (1998).
  Article CAS PubMed Google Scholar
• Lagerstrom, M. C. et al. VGLUT2-dependent sensory neurons in the TRPV1 population regulate pain and itch. Neuron 68, 529–542 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Liu, Y. et al. VGLUT2-dependent glutamate release from nociceptors is required to sense pain and suppress itch. Neuron 68, 543–556 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Bodo, E. et al. A hot new twist to hair biology: involvement of vanilloid receptor-1 (VR1/TRPV1) signaling in human hair growth control. Am. J. Pathol. 166, 985–998 (2005). This study was the first to show that TRPV1 expressed on non-neuronal skin cells is involved in the regulation of cell growth.
  Article CAS PubMed PubMed Central Google Scholar
• Toth, B. I. et al. Endocannabinoids modulate human epidermal keratinocyte proliferation and survival via the sequential engagement of cannabinoid receptor-1 and transient receptor potential Vanilloid-1. J. Invest. Dermatol. 131, 1095–1104 (2011).
  Article CAS PubMed Google Scholar
• Denda, M., Sokabe, T., Fukumi-Tominaga, T. & Tominaga, M. Effects of skin surface temperature on epidermal permeability barrier homeostasis. J. Invest. Dermatol. 127, 654–659 (2007).
  Article CAS PubMed Google Scholar
• Lee, Y. M., Kim, Y. K. & Chung, J. H. Increased expression of TRPV1 channel in intrinsically aged and photoaged human skin in vivo. Exp. Dermatol. 18, 431–436 (2009).
  Article CAS PubMed Google Scholar
• Lee, Y. M. et al. A novel role for the TRPV1 channel in UV-induced matrix metalloproteinase (MMP)-1 expression in HaCaT cells. J. Cell Physiol. 219, 766–775 (2009).
  Article CAS PubMed Google Scholar
• Peier, A. M. et al. A heat-sensitive TRP channel expressed in keratinocytes. Science 296, 2046–2049 (2002).
  Article CAS PubMed Google Scholar
• Asakawa, M. et al. Association of a mutation in TRPV3 with defective hair growth in rodents. J. Invest. Dermatol. 126, 2664–2672 (2006).
  Article CAS PubMed Google Scholar
• Yoshioka, T. et al. Impact of the Gly573Ser substitution in TRPV3 on the development of allergic and pruritic dermatitis in mice. J. Invest. Dermatol. 129, 714–722 (2009). These experiments demonstrated that a gain-of-function mutation in the Trpv3 gene results in severe dermatitis in mice; the TRPV3 protein is abundant in keratinocytes.
  Article CAS PubMed Google Scholar
• Borbiro, I., Geczy, T., Paus, R., Kovacs, L. & Biro, T. Activation of transient receptor potential vanilloid-3 (TRPV3) inhibits human hair growth. J. Invest. Dermatol. 128, S151 (2008).
  Article CAS Google Scholar
• Mazzone, S. B. & Undem, B. J. Cough sensors. V. Pharmacological modulation of cough sensors. Handb. Exp. Pharmacol. 187, 99–127 (2009).
  Article CAS Google Scholar
• Carr, M. J. & Lee, L. Y. Plasticity of peripheral mechanisms of cough. Respir. Physiol. Neurobiol. 152, 298–311 (2006).
  Article PubMed Google Scholar
• Fujimura, M. et al. Prostanoids and cough response to capsaicin in asthma and chronic bronchitis. Eur. Respir. J. 8, 1499–1505 (1995).
  CAS PubMed Google Scholar
• Blom, H. M. et al. Intranasal capsaicin is efficacious in non-allergic, non-infectious perennial rhinitis. A placebo-controlled study. Clin. Exp. Allergy 27, 796–801 (1997).
  Article CAS PubMed Google Scholar
• Matta, J. A. et al. General anesthetics activate a nociceptive ion channel to enhance pain and inflammation. Proc. Natl Acad. Sci. USA 105, 8784–8789 (2008).
  Article PubMed PubMed Central Google Scholar
• Andrè, E. et al. Cigarette smoke-induced neurogenic inflammation is mediated by α,β-unsaturated aldehydes and the TRPA1 receptor in rodents. J. Clin. Invest. 118, 2574–2582 (2008).
  PubMed PubMed Central Google Scholar
• Birrell, M. A. et al. TRPA1 agonists evoke coughing in guinea pig and human volunteers. Am. J. Respir. Crit. Care Med. 180, 1042–1047 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Talavera, K. et al. Nicotine activates the chemosensory cation channel TRPA1. Nature Neurosci. 12, 1293–1299 (2009).
  Article CAS PubMed Google Scholar
• Caceres, A. I. et al. A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma. Proc. Natl Acad. Sci. USA 106, 9099–9104 (2009).
  Article PubMed PubMed Central Google Scholar
• Nassini, R. et al. Acetaminophen, via its reactive metabolite _N_-acetyl-p-benzo-quinoneimine and transient receptor potential ankyrin-1 stimulation, causes neurogenic inflammation in the airways and other tissues in rodents. FASEB J. 24, 4904–4916 (2010).
  Article CAS PubMed Google Scholar
• Weissmann, N. et al. Classical transient receptor potential channel 6 (TRPC6) is essential for hypoxic pulmonary vasoconstriction and alveolar gas exchange. Proc. Natl Acad. Sci. USA 103, 19093–19098 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Yu, Y. et al. A functional single-nucleotide polymorphism in the TRPC6 gene promoter associated with idiopathic pulmonary arterial hypertension. Circulation 119, 2313–2322 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• White, T. A. et al. Role of transient receptor potential C3 in TNF-α-enhanced calcium influx in human airway myocytes. Am. J. Respir. Cell. Mol. Biol. 35, 243–251 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Xiao, J. H., Zheng, Y. M., Liao, B. & Wang, Y. X. Functional role of canonical transient receptor potential 1 and canonical transient receptor potential 3 in normal and asthmatic airway smooth muscle cells. Am. J. Respir. Cell Mol. Biol. 43, 17–25 (2010).
  Article CAS PubMed Google Scholar
• Sel, S. et al. Loss of classical transient receptor potential 6 channel reduces allergic airway response. Clin. Exp. Allergy 38, 1548–1558 (2008).
  Article CAS PubMed Google Scholar
• Jia, Y. et al. Functional TRPV4 channels are expressed in human airway smooth muscle cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 287, L272–L278 (2004).
  Article CAS PubMed Google Scholar
• Zhu, G. et al. Association of TRPV4 gene polymorphisms with chronic obstructive pulmonary disease. Hum. Mol. Genet. 18, 2053–2062 (2009). This was the first study to suggest that TRPV4 can regulate lung function in humans.
  Article CAS PubMed Google Scholar
• Li, J. et al. TRPV4-mediated calcium-influx into human bronchial epithelia upon exposure to diesel exhaust particles. Environ. Health Perspect. 119, 784–793 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Jian, M. Y., King, J. A., Al-Mehdi, A. B., Liedtke, W. & Townsley, M. I. High vascular pressure-induced lung injury requires P450 epoxygenase-dependent activation of TRPV4. Am. J. Respir. Cell Mol. Biol. 38, 386–392 (2008).
  Article CAS PubMed Google Scholar
• Hamanaka, K. et al. TRPV4 initiates the acute calcium-dependent permeability increase during ventilator-induced lung injury in isolated mouse lungs. Am. J. Physiol. Lung Cell. Mol. Physiol. 293, L923–L932 (2007).
  Article CAS PubMed Google Scholar
• Willette, R. N. et al. Systemic activation of the transient receptor potential vanilloid subtype 4 channel causes endothelial failure and circulatory collapse: part 2. J. Pharmacol. Exp. Ther. 326, 443–452 (2008).
  Article CAS PubMed Google Scholar
• Hamanaka, K. et al. TRPV4 channels augment macrophage activation and ventilator-induced lung injury. Am. J. Physiol. Lung Cell. Mol. Physiol. 299, L353–L362 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Mizoguchi, F. et al. Transient receptor potential vanilloid 4 deficiency suppresses unloading-induced bone loss. J. Cell Physiol. 216, 47–53 (2008).
  Article CAS PubMed Google Scholar
• Masuyama, R. et al. TRPV4-mediated calcium influx regulates terminal differentiation of osteoclasts. Cell. Metab. 8, 257–265 (2008).
  Article CAS PubMed Google Scholar
• Dai, J. et al. Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family. J. Med. Genet. 47, 704–709 (2010).
  Article CAS PubMed Google Scholar
• Rock, M. J. et al. Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia. Nature Genet. 40, 999–1003 (2008).
  Article CAS PubMed Google Scholar
• Krakow, D. et al. Mutations in the gene encoding the calcium-permeable ion channel TRPV4 produce spondylometaphyseal dysplasia, Kozlowski type and metatropic dysplasia. Am. J. Hum. Genet. 84, 307–315 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Auer-Grumbach, M. et al. Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C. Nature Genet. 42, 160–164 (2010).
  Article CAS PubMed Google Scholar
• Landoure, G. et al. Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C. Nature Genet. 42, 170–174 (2010).
  Article CAS PubMed Google Scholar
• Feng, S. et al. Identification and functional characterization of an N-terminal oligomerization domain for polycystin-2. J. Biol. Chem. 283, 28471–28479 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Nauli, S. M. et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nature Genet. 33, 129–137 (2003).
  Article CAS PubMed Google Scholar
• Sharif-Naeini, R. et al. Polycystin-1 and -2 dosage regulates pressure sensing. Cell 139, 587–596 (2009).
  Article CAS PubMed Google Scholar
• Winn, M. P. et al. A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science 308, 1801–1804 (2005).
  Article CAS PubMed Google Scholar
• Moller, C. C. et al. Induction of TRPC6 channel in acquired forms of proteinuric kidney disease. J. Am. Soc. Nephrol. 18, 29–36 (2007).
  Article CAS PubMed Google Scholar
• Reiser, J. et al. TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function. Nature Genet. 37, 739–744 (2005).
  Article CAS PubMed Google Scholar
• Wang, Y. et al. Activation of NFAT signaling in podocytes causes glomerulosclerosis. J. Am. Soc. Nephrol. 21, 1657–1666 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Chubanov, V. et al. Hypomagnesemia with secondary hypocalcemia due to a missense mutation in the putative pore-forming region of TRPM6. J. Biol. Chem. 282, 7656–7667 (2007).
  Article CAS PubMed Google Scholar
• Schlingmann, K. P. et al. Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. Nature Genet. 31, 166–170 (2002).
  Article CAS PubMed Google Scholar
• Schlingmann, K. P. et al. Novel TRPM6 mutations in 21 families with primary hypomagnesemia and secondary hypocalcemia. J. Am. Soc. Nephrol. 16, 3061–3069 (2005).
  Article PubMed Google Scholar
• Dong, X. P. et al. The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel. Nature 455, 992–996 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Szallasi, A. & Di Marzo, V. New perspectives on enigmatic vanilloid receptors. Trends Neurosci. 23, 491–497 (2000).
  Article CAS PubMed Google Scholar
• Cavanaugh, D. et al. Trpv1 reporter mice reveal highly restricted brain distribution and functional expression in arteriolar smooth muscle. J. Neurosci. 31, 5067–5077 (2011). This careful study highlighted the challenges of determining the expression pattern for a target of interest, and the need to combine multiple approaches.
  Article CAS PubMed PubMed Central Google Scholar
• Marsch, R. et al. Reduced anxiety, conditioned fear, and hippocampal long-term potentiation in transient receptor potential vanilloid type 1 receptor-deficient mice. J. Neurosci. 27, 832–839 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Mezey, E. et al. Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human. Proc. Natl Acad. Sci. USA 97, 3655–3660 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Kauer, J. A. & Gibson, H. E. Hot flash: TRPV channels in the brain. Trends Neurosci. 32, 215–224 (2009).
  Article CAS PubMed Google Scholar
• Grueter, B. A., Brasnjo, G. & Malenka, R. C. Postsynaptic TRPV1 triggers cell type-specific long-term depression in the nucleus accumbens. Nature Neurosci. 13, 1519–1525 (2010).
  Article CAS PubMed Google Scholar
• Jia, Y., Zhou, J., Tai, Y. & Wang, Y. TRPC channels promote cerebellar granule neuron survival. Nature Neurosci. 10, 559–567 (2007).
  Article CAS PubMed Google Scholar
• Hartmann, J. et al. TRPC3 channels are required for synaptic transmission and motor coordination. Neuron 59, 392–398 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Becker, E. B. et al. A point mutation in TRPC3 causes abnormal Purkinje cell development and cerebellar ataxia in moonwalker mice. Proc. Natl Acad. Sci. USA 106, 6706–6711 (2009).
  Article PubMed PubMed Central Google Scholar
• Riccio, A. et al. Essential role for TRPC5 in amygdala function and fear-related behavior. Cell 137, 761–772 (2009). This study was the first to implicate TRPC5 in anxiety. The neuronal recordings obtained in the study suggest that there is a potential link between TRPC5 and the CCK4 pathway.
  Article CAS PubMed PubMed Central Google Scholar
• Greka, A., Navarro, B., Oancea, E., Duggan, A. & Clapham, D. E. TRPC5 is a regulator of hippocampal neurite length and growth cone morphology. Nature Neurosci. 6, 837–845 (2003).
  Article CAS PubMed Google Scholar
• Miller, B. A. & Zhang, W. TRP channels as mediators of oxidative stress. Adv. Exp. Med. Biol. 704, 531–544 (2011).
  Article CAS PubMed Google Scholar
• Xu, C. et al. TRPM2 variants and bipolar disorder risk: confirmation in a family-based association study. Bipolar Disord. 11, 1–10 (2009).
  Article PubMed Google Scholar
• Aarts, M. et al. A key role for TRPM7 channels in anoxic neuronal death. Cell 115, 863–877 (2003).
  Article CAS PubMed Google Scholar
• Lehen'kyi, V. & Prevarskaya, N. Oncogenic TRP channels. Adv. Exp. Med. Biol. 704, 929–945 (2011).
  Article CAS PubMed Google Scholar
• Tsavaler, L., Shapero, M. H., Morkowski, S. & Laus, R. Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins. Cancer Res. 61, 3760–3769 (2001).
  CAS PubMed Google Scholar
• Thebault, S. et al. Novel role of cold/menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activation of store-operated channels in LNCaP human prostate cancer epithelial cells. J. Biol. Chem. 280, 39423–39435 (2005).
  Article CAS PubMed Google Scholar
• Reading, S. A. & Brayden, J. E. Central role of TRPM4 channels in cerebral blood flow regulation. Stroke 38, 2322–2328 (2007).
  Article CAS PubMed Google Scholar
• Kruse, M. et al. Impaired endocytosis of the ion channel TRPM4 is associated with human progressive familial heart block type I. J. Clin. Invest. 119, 2737–2744 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Liu, H. et al. Gain-of-function mutations in TRPM4 cause autosomal dominant isolated cardiac conduction disease. Circ. Cardiovasc. Genet. 3, 374–385 (2010).
  Article CAS PubMed Google Scholar
• Mathar, I. et al. Increased catecholamine secretion contributes to hypertension in TRPM4-deficient mice. J. Clin. Invest. 120, 3267–3279 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Onohara, N. et al. TRPC3 and TRPC6 are essential for angiotensin II-induced cardiac hypertrophy. EMBO J. 25, 5305–5316 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Brixel, L. R. et al. TRPM5 regulates glucose-stimulated insulin secretion. Pflugers Arch. 460, 69–76 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Colsoul, B. et al. Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5 −/− mice. Proc. Natl Acad. Sci. USA 107, 5208–5213 (2010). This study identified TRPM5 as a potential target for antidiabetic drugs.
  Article PubMed PubMed Central Google Scholar
• Suri, A. & Szallasi, A. The emerging role of TRPV1 in diabetes and obesity. Trends Pharmacol. Sci. 29, 29–36 (2008).
  Article CAS PubMed Google Scholar
• Motter, A. L. & Ahern, G. P. TRPV1-null mice are protected from diet-induced obesity. FEBS Lett. 582, 2257–2262 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Biro, T. et al. Hair cycle control by vanilloid receptor-1 (TRPV1): evidence from TRPV1 knockout mice. J. Invest. Dermatol. 126, 1909–1912 (2006).
  Article CAS PubMed Google Scholar
• Toth, B. I. et al. Transient receptor potential vanilloid-1 signaling as a regulator of human sebocyte biology. J. Invest. Dermatol. 129, 329–339 (2009).
  Article CAS PubMed Google Scholar
• Beck, B. et al. TRPC channels determine human keratinocyte differentiation: new insight into basal cell carcinoma. Cell Calcium 43, 492–505 (2008).
  Article CAS PubMed Google Scholar
• Pani, B. et al. Up-regulation of transient receptor potential canonical 1 (TRPC1) following sarco(endo)plasmic reticulum Ca2+ ATPase 2 gene silencing promotes cell survival: a potential role for TRPC1 in Darier's disease. Mol. Biol. Cell 17, 4446–4458 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Atoyan, R., Shander, D. & Botchkareva, N. V. Non-neuronal expression of transient receptor potential type A1 (TRPA1) in human skin. J. Invest. Dermatol. 129, 2312–2315 (2009).
  Article CAS PubMed Google Scholar
• Lehen'kyi, V. et al. TRPV6 is a Ca2+ entry channel essential for Ca2+-induced differentiation of human keratinocytes. J. Biol. Chem. 282, 22582–22591 (2007).
  Article CAS PubMed Google Scholar
• McNeill, M. S. et al. Cell death of melanophores in zebrafish trpm7 mutant embryos depends on melanin synthesis. J. Invest. Dermatol. 127, 2020–2030 (2007).
  Article CAS PubMed Google Scholar
• Kiyonaka, S. et al. Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound. Proc. Natl Acad. Sci. USA 106, 5400–5405 (2009).
  Article PubMed PubMed Central Google Scholar
• Venkatachalam, K. et al. Motor deficit in a Drosophila model of mucolipidosis type IV due to defective clearance of apoptotic cells. Cell 135, 838–851 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Lambert, S. et al. Transient receptor potential melastatin 1 (TRPM1) is an ion-conducting plasma membrane channel inhibited by zinc ions. J. Biol. Chem. 286, 12221–12233 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Bellone, R. R. et al. Differential gene expression of TRPM1, the potential cause of congenital stationary night blindness and coat spotting patterns (LP) in the Appaloosa horse (Equus caballus). Genetics 179, 1861–1870 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Audo, I. et al. TRPM1 is mutated in patients with autosomal-recessive complete congenital stationary night blindness. Am. J. Hum. Genet. 85, 720–729 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Li, Z. et al. Recessive mutations of the gene TRPM1 abrogate ON bipolar cell function and cause complete congenital stationary night blindness in humans. Am. J. Hum. Genet. 85, 711–719 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• van Genderen, M. M. et al. Mutations in TRPM1 are a common cause of complete congenital stationary night blindness. Am. J. Hum. Genet. 85, 730–736 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Uchida, K. et al. Lack of TRPM2 impaired insulin secretion and glucose metabolisms in mice. Diabetes 60, 119–126 (2011).
  Article CAS PubMed Google Scholar
• Harteneck, C., Frenzel, H. & Kraft, R. _N_-(p-amylcinnamoyl)anthranilic acid (ACA): a phospholipase A(2) inhibitor and TRP channel blocker. Cardiovasc. Drug Rev. 25, 61–75 (2007).
  Article CAS PubMed Google Scholar
• Walder, R. Y. et al. Mice defective in Trpm6 show embryonic mortality and neural tube defects. Hum. Mol. Genet. 18, 4367–4375 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Jin, J. et al. Deletion of Trpm7 disrupts embryonic development and thymopoiesis without altering Mg2+ homeostasis. Science 322, 756–760 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Hermosura, M. C. et al. A TRPM7 variant shows altered sensitivity to magnesium that may contribute to the pathogenesis of two Guamanian neurodegenerative disorders. Proc. Natl Acad. Sci. USA 102, 11510–11515 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Chen, H. C. et al. Blockade of TRPM7 channel activity and cell death by inhibitors of 5-lipoxygenase. PLoS ONE 5, e11161 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Higashi, Y., Kiuchi, T. & Furuta, K. Efficacy and safety profile of a topical methyl salicylate and menthol patch in adult patients with mild to moderate muscle strain: a randomized, double-blind, parallel-group, placebo-controlled, multicenter study. Clin. Ther. 32, 34–43 (2010).
  Article CAS PubMed Google Scholar
• Garcia-Gonzalez, M. A. et al. Pkd1 and Pkd2 are required for normal placental development. PLoS ONE 5, e12821 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Clapham, D. E. TRP channels as cellular sensors. Nature 426, 517–524 (2003).
  Article CAS PubMed Google Scholar
• Scholz, J. & Clifford, J. W. Can we conquer pain? Nature Neurosci. 5, 1062–1067 (2002).
  Article CAS PubMed Google Scholar