Skip to main content
SpringerLink
Log in

TRPV1

  • Chapter
  • First Online:
Mammalian Transient Receptor Potential (TRP) Cation Channels

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 222))

Abstract

TRPV1 is a well-characterised channel expressed by a subset of peripheral sensory neurons involved in pain sensation and also at a number of other neuronal and non-neuronal sites in the mammalian body. Functionally, TRPV1 acts as a sensor for noxious heat (greater than ~42 °C). It can also be activated by some endogenous lipid-derived molecules, acidic solutions (pH < 6.5) and some pungent chemicals and food ingredients such as capsaicin, as well as by toxins such as resiniferatoxin and vanillotoxins. Structurally, TRPV1 subunits have six transmembrane (TM) domains with intracellular N- (containing 6 ankyrin-like repeats) and C-termini and a pore region between TM5 and TM6 containing sites that are important for channel activation and ion selectivity. The N- and C- termini have residues and regions that are sites for phosphorylation/dephosphorylation and PI(4,5)P2 binding, which regulate TRPV1 sensitivity and membrane insertion. The channel has several interacting proteins, some of which (e.g. AKAP79/150) are important for TRPV1 phosphorylation. Four TRPV1 subunits form a non-selective, outwardly rectifying ion channel permeable to monovalent and divalent cations with a single-channel conductance of 50–100 pS. TRPV1 channel kinetics reveal multiple open and closed states, and several models for channel activation by voltage, ligand binding and temperature have been proposed. Studies with TRPV1 agonists and antagonists and Trpv1 −/− mice have suggested a role for TRPV1 in pain, thermoregulation and osmoregulation, as well as in cough and overactive bladder. TRPV1 antagonists have advanced to clinical trials where findings of drug-induced hyperthermia and loss of heat sensitivity have raised questions about the viability of this therapeutic approach.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ahern GP, Premkumar LS (2002) Voltage-dependent priming of rat vanilloid receptor: effects of agonist and protein kinase C activation. J Physiol 545(Pt 2):441–451

    PubMed Central  PubMed  CAS  Google Scholar 

  • Ahern GP, Brooks IM, Miyares RL, Wang XB (2005) Extracellular cations sensitize and gate capsaicin receptor TRPV1 modulating pain signaling. J Neurosci 25(21):5109–5116

    PubMed  CAS  Google Scholar 

  • Ahern GP, Wang X, Miyares RL (2006) Polyamines are potent ligands for the capsaicin receptor TRPV1. J Biol Chem 281(13):8991–8995

    PubMed  CAS  Google Scholar 

  • Amadesi S, Cottrell GS, Divino L, Chapman K, Grady EF, Bautista F et al (2006) Protease-activated receptor 2 sensitizes TRPV1 by protein kinase C epsilon- and A-dependent mechanisms in rats and mice. J Physiol 575(Pt 2):555–571

    PubMed Central  PubMed  CAS  Google Scholar 

  • Banke TG, Chaplan SR, Wickenden AD (2010) Dynamic changes in the TRPA1 selectivity filter lead to progressive but reversible pore dilation. Am J Physiol Cell Physiol 298(6):C1457–C1468

    PubMed  CAS  Google Scholar 

  • Baumann TK, Martenson ME (2000) Extracellular protons both increase the activity and reduce the conductance of capsaicin- gated channels. J Neurosci 20(11):RC80

    PubMed  CAS  Google Scholar 

  • Bevan S, Szolcsanyi J (1990) Sensory neuron-specific actions of capsaicin: mechanisms and applications. Trends Pharmacol Sci 11(8):330–333

    PubMed  CAS  Google Scholar 

  • Bevan S, Winter J (1995) Nerve growth factor (NGF) differentially regulates the chemosensitivity of adult rat cultured sensory neurons. J Neurosci 15(7 Pt 1):4918–4926

    PubMed  CAS  Google Scholar 

  • Bevan S, Yeats J (1991) Protons activate a cation conductance in a sub-population of rat dorsal root ganglion neurones. J Physiol 433:145–161

    PubMed Central  PubMed  CAS  Google Scholar 

  • Bevan S, Hothi S, Hughes G, James IF, Rang HP, Shah K et al (1992) Capsazepine: a competitive antagonist of the sensory neurone excitant capsaicin. Br J Pharmacol 107(2):544–552

    PubMed Central  PubMed  CAS  Google Scholar 

  • Bhattacharya A, Scott BP, Nasser N, Ao H, Maher MP, Dubin AE et al (2007) Pharmacology and antitussive efficacy of 4-(3-trifluoromethyl-pyridin-2-yl)-piperazine-1-carboxylic acid (5-trifluoromethyl-pyridin-2-yl)-amide (JNJ17203212), a transient receptor potential vanilloid 1 antagonist in guinea pigs. J Pharmacol Exp Ther 323(2):665–674

    PubMed  CAS  Google Scholar 

  • Bhave G, Zhu W, Wang H, Brasier DJ, Oxford GS, Gereau RW 4th (2002) cAMP-dependent protein kinase regulates desensitization of the capsaicin receptor (VR1) by direct phosphorylation. Neuron 35(4):721–731

    PubMed  CAS  Google Scholar 

  • Bhave G, Hu HJ, Glauner KS, Zhu W, Wang H, Brasier DJ et al (2003) Protein kinase C phosphorylation sensitizes but does not activate the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1). Proc Natl Acad Sci USA 100(21):12480–12485

    PubMed Central  PubMed  CAS  Google Scholar 

  • Binder A, May D, Baron R, Maier C, Tolle TR, Treede RD et al (2011) Transient receptor potential channel polymorphisms are associated with the somatosensory function in neuropathic pain patients. PLoS One 6(3):e17387

    PubMed Central  PubMed  CAS  Google Scholar 

  • Binshtok AM, Bean BP, Woolf CJ (2007) Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockers. Nature 449(7162):607–610

    PubMed  CAS  Google Scholar 

  • Birder LA, Nakamura Y, Kiss S, Nealen ML, Barrick S, Kanai AJ et al (2002) Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat Neurosci 5(9):856–860

    PubMed  CAS  Google Scholar 

  • Birnbaumer L, Yildirim E, Abramowitz J (2003) A comparison of the genes coding for canonical TRP channels and their M, V and P relatives. Cell Calcium 33(5–6):419–432

    PubMed  CAS  Google Scholar 

  • Bohlen CJ, Julius D (2012) Receptor-targeting mechanisms of pain-causing toxins: how ow? Toxicon 60(3):254–264

    PubMed Central  PubMed  CAS  Google Scholar 

  • Bohlen CJ, Priel A, Zhou S, King D, Siemens J, Julius D (2010) A bivalent tarantula toxin activates the capsaicin receptor, TRPV1, by targeting the outer pore domain. Cell 141(5):834–845

    PubMed Central  PubMed  CAS  Google Scholar 

  • Bolcskei K, Helyes Z, Szabo A, Sandor K, Elekes K, Nemeth J et al (2005) Investigation of the role of TRPV1 receptors in acute and chronic nociceptive processes using gene-deficient mice. Pain 117(3):368–376

    PubMed  Google Scholar 

  • Bonnington JK, McNaughton PA (2003) Signalling pathways involved in the sensitisation of mouse nociceptive neurones by nerve growth factor. J Physiol 551(Pt 2):433–446

    PubMed Central  PubMed  CAS  Google Scholar 

  • Brandao KE, Dell'Acqua ML, Levinson SR (2012) A-kinase anchoring protein 150 expression in a specific subset of TRPV1- and CaV 1.2-positive nociceptive rat dorsal root ganglion neurons. J Comp Neurol 520(1):81–99

    PubMed  CAS  Google Scholar 

  • Brauchi S, Orio P, Latorre R (2004) Clues to understanding cold sensation: thermodynamics and electrophysiological analysis of the cold receptor TRPM8. Proc Natl Acad Sci USA 101(43):15494–15499

    PubMed Central  PubMed  CAS  Google Scholar 

  • Brauchi S, Orta G, Salazar M, Rosenmann E, Latorre R (2006) A hot-sensing cold receptor: C-terminal domain determines thermosensation in transient receptor potential channels. J Neurosci 26(18):4835–4840

    PubMed  CAS  Google Scholar 

  • Brauchi S, Orta G, Mascayano C, Salazar M, Raddatz N, Urbina H et al (2007) Dissection of the components for PIP2 activation and thermosensation in TRP channels. Proc Natl Acad Sci USA 104(24):10246–10251

    PubMed Central  PubMed  CAS  Google Scholar 

  • Breza JM, Contreras RJ (2012) Anion size modulates salt taste in rats. J Neurophysiol 107(6):1632–1648

    PubMed Central  PubMed  CAS  Google Scholar 

  • Bron R, Klesse LJ, Shah K, Parada LF, Winter J (2003) Activation of Ras is necessary and sufficient for upregulation of vanilloid receptor type 1 in sensory neurons by neurotrophic factors. Mol Cell Neurosci 22(1):118–132

    PubMed  CAS  Google Scholar 

  • Btesh J, Fischer MJ, Stott K, McNaughton PA (2013) Mapping the binding site of TRPV1 on AKAP79: implications for inflammatory hyperalgesia. J Neurosci 33(21):9184–9193

    PubMed  CAS  Google Scholar 

  • Camprubi-Robles M, Planells-Cases R, Ferrer-Montiel A (2009) Differential contribution of SNARE-dependent exocytosis to inflammatory potentiation of TRPV1 in nociceptors. FASEB J 23(11):3722–3733

    PubMed  CAS  Google Scholar 

  • Cantero-Recasens G, Gonzalez JR, Fandos C, Duran-Tauleria E, Smit LA, Kauffmann F et al (2010) Loss of function of transient receptor potential vanilloid 1 (TRPV1) genetic variant is associated with lower risk of active childhood asthma. J Biol Chem 285(36):27532–27535

    PubMed Central  PubMed  CAS  Google Scholar 

  • Cao E, Cordero-Morales JF, Liu B, Qin F, Julius D (2013a) TRPV1 channels are intrinsically heat sensitive and negatively regulated by phosphoinositide lipids. Neuron 77(4):667–679

    PubMed Central  PubMed  CAS  Google Scholar 

  • Cao E, Liao M, Cheng Y, Julius D (2013b) TRPV1 structures in distinct conformations reveal activation mechanisms. Nature 504(7478):113–118

    PubMed  CAS  Google Scholar 

  • Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389(6653):816–824

    PubMed  CAS  Google Scholar 

  • Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR et al (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288(5464):306–313

    PubMed  CAS  Google Scholar 

  • Cavanaugh DJ, Chesler AT, Jackson AC, Sigal YM, Yamanaka H, Grant R et al (2011) Trpv1 reporter mice reveal highly restricted brain distribution and functional expression in arteriolar smooth muscle cells. J Neurosci 31(13):5067–5077

    PubMed Central  PubMed  CAS  Google Scholar 

  • Cesare P, McNaughton P (1996) A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin. Proc Natl Acad Sci USA 93(26):15435–15439

    PubMed Central  PubMed  CAS  Google Scholar 

  • Charrua A, Cruz CD, Narayanan S, Gharat L, Gullapalli S, Cruz F et al (2009) GRC-6211, a new oral specific TRPV1 antagonist, decreases bladder overactivity and noxious bladder input in cystitis animal models. J Urol 181(1):379–386

    PubMed  CAS  Google Scholar 

  • Chavez AE, Chiu CQ, Castillo PE (2010) TRPV1 activation by endogenous anandamide triggers postsynaptic long-term depression in dentate gyrus. Nat Neurosci 13(12):1511–1518

    PubMed Central  PubMed  CAS  Google Scholar 

  • Chuang HH, Prescott ED, Kong H, Shields S, Jordt SE, Basbaum AI et al (2001) Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature 411(6840):957–962

    PubMed  CAS  Google Scholar 

  • Chung MK, Lee H, Mizuno A, Suzuki M, Caterina MJ (2004) TRPV3 and TRPV4 mediate warmth-evoked currents in primary mouse keratinocytes. J Biol Chem 279(20):21569–21575

    PubMed  CAS  Google Scholar 

  • Chung MK, Guler AD, Caterina MJ (2005) Biphasic currents evoked by chemical or thermal activation of the heat-gated ion channel, TRPV3. J Biol Chem 280(16):15928–15941

    PubMed  CAS  Google Scholar 

  • Chung MK, Guler AD, Caterina MJ (2008) TRPV1 shows dynamic ionic selectivity during agonist stimulation. Nat Neurosci 11(5):555–564

    PubMed  CAS  Google Scholar 

  • Ciura S, Bourque CW (2006) Transient receptor potential vanilloid 1 is required for intrinsic osmoreception in organum vasculosum lamina terminalis neurons and for normal thirst responses to systemic hyperosmolality. J Neurosci 26(35):9069–9075

    PubMed  CAS  Google Scholar 

  • Cui M, Honore P, Zhong C, Gauvin D, Mikusa J, Hernandez G et al (2006) TRPV1 receptors in the CNS play a key role in broad-spectrum analgesia of TRPV1 antagonists. J Neurosci 26(37):9385–9393

    PubMed  CAS  Google Scholar 

  • Dai Y, Moriyama T, Higashi T, Togashi K, Kobayashi K, Yamanaka H et al (2004) Proteinase-activated receptor 2-mediated potentiation of transient receptor potential vanilloid subfamily 1 activity reveals a mechanism for proteinase-induced inflammatory pain. J Neurosci 24(18):4293–4299

    PubMed  CAS  Google Scholar 

  • Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, Overend P et al (2000) Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405(6783):183–187

    PubMed  CAS  Google Scholar 

  • De-la-Rosa V, Rangel-Yescas GE, Ladron-de-Guevara E, Rosenbaum T, Islas LD (2013) Coarse architecture of the transient receptor potential vanilloid 1 (TRPV1) ion channel determined by fluorescence resonance energy transfer. J Biol Chem 288(41):29506–29517

    PubMed  CAS  Google Scholar 

  • Delescluse I, Mace H, Adcock JJ (2012) Inhibition of airway hyper-responsiveness by TRPV1 antagonists (SB-705498 and PF-04065463) in the unanaesthetized, ovalbumin-sensitized guinea pig. Br J Pharmacol 166(6):1822–1832

    PubMed Central  PubMed  CAS  Google Scholar 

  • Delmas P, Brown DA (2005) Pathways modulating neural KCNQ/M (Kv7) potassium channels. Nat Rev Neurosci 6(11):850–862

    PubMed  CAS  Google Scholar 

  • Docherty RJ, Yeats JC, Bevan S, Boddeke HW (1996) Inhibition of calcineurin inhibits the desensitization of capsaicin-evoked currents in cultured dorsal root ganglion neurones from adult rats. Pflugers Arch 431(6):828–837

    PubMed  CAS  Google Scholar 

  • Efendiev R, Bavencoffe A, Hu H, Zhu MX, Dessauer CW (2013) Scaffolding by A-kinase anchoring protein enhances functional coupling between adenylyl cyclase and TRPV1 channel. J Biol Chem 288(6):3929–3937

    PubMed Central  PubMed  CAS  Google Scholar 

  • Egan TM, Khakh BS (2004) Contribution of calcium ions to P2X channel responses. J Neurosci 24(13):3413–3420

    PubMed  CAS  Google Scholar 

  • Eid SR (2011) Therapeutic targeting of TRP channels–the TR(i)P to pain relief. Curr Top Med Chem 11(17):2118–2130

    PubMed  CAS  Google Scholar 

  • Eilers H, Lee SY, Hau CW, Logvinova A, Schumacher MA (2007) The rat vanilloid receptor splice variant VR.5’sv blocks TRPV1 activation. Neuroreport 18(10):969–973

    PubMed  CAS  Google Scholar 

  • Everaerts W, Sepulveda MR, Gevaert T, Roskams T, Nilius B, De Ridder D (2009) Where is TRPV1 expressed in the bladder, do we see the real channel? Naunyn Schmiedebergs Arch Pharmacol 379(4):421–425

    PubMed  CAS  Google Scholar 

  • Firner M, Greffrath W, Treede RD (2006) Phosphorylation of extracellular signal-related protein kinase is required for rapid facilitation of heat-induced currents in rat dorsal root ganglion neurons. Neuroscience 143(1):253–263

    PubMed  CAS  Google Scholar 

  • Fischer MJ, Btesh J, McNaughton PA (2013) Disrupting sensitization of transient receptor potential vanilloid subtype 1 inhibits inflammatory hyperalgesia. J Neurosci 33(17):7407–7414

    PubMed  CAS  Google Scholar 

  • Garami A, Shimansky YP, Pakai E, Oliveira DL, Gavva NR, Romanovsky AA (2010) Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia. J Neurosci 30(4):1435–1440

    PubMed Central  PubMed  CAS  Google Scholar 

  • Garcia-Martinez C, Morenilla-Palao C, Planells-Cases R, Merino JM, Ferrer-Montiel A (2000) Identification of an aspartic residue in the P-loop of the vanilloid receptor that modulates pore properties. J Biol Chem 275(42):32552–32558

    PubMed  CAS  Google Scholar 

  • Gavva NR, Klionsky L, Qu Y, Shi L, Tamir R, Edenson S et al (2004) Molecular determinants of vanilloid sensitivity in TRPV1. J Biol Chem 279(19):20283–20295

    PubMed  CAS  Google Scholar 

  • Gavva NR, Bannon AW, Surapaneni S, Hovland DN Jr, Lehto SG, Gore A et al (2007) The vanilloid receptor TRPV1 is tonically activated in vivo and involved in body temperature regulation. J Neurosci 27(13):3366–3374

    PubMed  CAS  Google Scholar 

  • Gavva NR, Treanor JJ, Garami A, Fang L, Surapaneni S, Akrami A et al (2008) Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans. Pain 136(1–2):202–210

    PubMed  CAS  Google Scholar 

  • Ghilardi JR, Rohrich H, Lindsay TH, Sevcik MA, Schwei MJ, Kubota K et al (2005) Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain. J Neurosci 25(12):3126–3131

    PubMed  CAS  Google Scholar 

  • Gracheva EO, Cordero-Morales JF, Gonzalez-Carcacia JA, Ingolia NT, Manno C, Aranguren CI et al (2011) Ganglion-specific splicing of TRPV1 underlies infrared sensation in vampire bats. Nature 476(7358):88–91

    PubMed Central  PubMed  CAS  Google Scholar 

  • Grandl J, Kim SE, Uzzell V, Bursulaya B, Petrus M, Bandell M et al (2010) Temperature-induced opening of TRPV1 ion channel is stabilized by the pore domain. Nat Neurosci 13(6):708–714

    PubMed Central  PubMed  CAS  Google Scholar 

  • Grueter BA, Brasnjo G, Malenka RC (2010) Postsynaptic TRPV1 triggers cell type-specific long-term depression in the nucleus accumbens. Nat Neurosci 13(12):1519–1525

    PubMed Central  PubMed  CAS  Google Scholar 

  • Grycova L, Lansky Z, Friedlova E, Obsilova V, Janouskova H, Obsil T et al (2008) Ionic interactions are essential for TRPV1 C-terminus binding to calmodulin. Biochem Biophys Res Commun 375(4):680–683

    PubMed  CAS  Google Scholar 

  • Hayes P, Meadows HJ, Gunthorpe MJ, Harries MH, Duckworth DM, Cairns W et al (2000) Cloning and functional expression of a human orthologue of rat vanilloid receptor-1. Pain 88(2):205–215

    PubMed  CAS  Google Scholar 

  • Helliwell RJ, McLatchie LM, Clarke M, Winter J, Bevan S, McIntyre P (1998) Capsaicin sensitivity is associated with the expression of the vanilloid (capsaicin) receptor (VR1) mRNA in adult rat sensory ganglia. Neurosci Lett 250(3):177–180

    PubMed  CAS  Google Scholar 

  • Hellwig N, Plant TD, Janson W, Schafer M, Schultz G, Schaefer M (2004) TRPV1 acts as proton channel to induce acidification in nociceptive neurons. J Biol Chem 279(33):34553–34561

    PubMed  CAS  Google Scholar 

  • Hille B (2001) Ion channels of excitable membranes, 3rd edn. Sinauer, Sunderland, MA

    Google Scholar 

  • Hirokawa N, Noda Y, Tanaka Y, Niwa S (2009) Kinesin superfamily motor proteins and intracellular transport. Nat Rev Mol Cell Biol 10(10):682–696

    PubMed  CAS  Google Scholar 

  • Holzer P (1991) Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol Rev 43(2):143–201

    PubMed  CAS  Google Scholar 

  • Honore P, Wismer CT, Mikusa J, Zhu CZ, Zhong C, Gauvin DM et al (2005) A-425619 [1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea], a novel transient receptor potential type V1 receptor antagonist, relieves pathophysiological pain associated with inflammation and tissue injury in rats. J Pharmacol Exp Ther 314(1):410–421

    PubMed  CAS  Google Scholar 

  • Huang SM, Bisogno T, Trevisani M, Al-Hayani A, De Petrocellis L, Fezza F et al (2002) An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors. Proc Natl Acad Sci USA 99(12):8400–8405

    PubMed Central  PubMed  CAS  Google Scholar 

  • Hui K, Liu B, Qin F (2003) Capsaicin activation of the pain receptor, VR1: multiple open states from both partial and full binding. Biophys J 84(5):2957–2968

    PubMed Central  PubMed  CAS  Google Scholar 

  • Hwang SW, Cho H, Kwak J, Lee SY, Kang CJ, Jung J et al (2000) Direct activation of capsaicin receptors by products of lipoxygenases: endogenous capsaicin-like substances. Proc Natl Acad Sci USA 97(11):6155–6160

    PubMed Central  PubMed  CAS  Google Scholar 

  • Immke DC, Gavva NR (2006) The TRPV1 receptor and nociception. Semin Cell Dev Biol 17(5):582–591

    PubMed  CAS  Google Scholar 

  • Inoue K, Koizumi S, Fuziwara S, Denda S, Inoue K, Denda M (2002) Functional vanilloid receptors in cultured normal human epidermal keratinocytes. Biochem Biophys Res Commun 291(1):124–129

    PubMed  CAS  Google Scholar 

  • Jancso-Gabor A, Szolcsanyi J, Jancso N (1970a) Irreversible impairment of thermoregulation induced by capsaicin and similar pungent substances in rats and guinea-pigs. J Physiol 206(3):495–507

    PubMed Central  PubMed  CAS  Google Scholar 

  • Jancso-Gabor A, Szolcsanyi J, Jancso N (1970b) Stimulation and desensitization of the hypothalamic heat-sensitive structures by capsaicin in rats. J Physiol 208(2):449–459

    PubMed Central  PubMed  CAS  Google Scholar 

  • Jara-Oseguera A, Llorente I, Rosenbaum T, Islas LD (2008) Properties of the inner pore region of TRPV1 channels revealed by block with quaternary ammoniums. J Gen Physiol 132(5):547–562

    PubMed Central  PubMed  CAS  Google Scholar 

  • Jeske NA, Diogenes A, Ruparel NB, Fehrenbacher JC, Henry M, Akopian AN et al (2008) A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1. Pain 138(3):604–616

    PubMed Central  PubMed  CAS  Google Scholar 

  • Jeske NA, Patwardhan AM, Ruparel NB, Akopian AN, Shapiro MS, Henry MA (2009) A-kinase anchoring protein 150 controls protein kinase C-mediated phosphorylation and sensitization of TRPV1. Pain 146(3):301–307

    PubMed Central  PubMed  CAS  Google Scholar 

  • Jeske NA, Por ED, Belugin S, Chaudhury S, Berg KA, Akopian AN et al (2011) A-kinase anchoring protein 150 mediates transient receptor potential family V type 1 sensitivity to phosphatidylinositol-4,5-bisphosphate. J Neurosci 31(23):8681–8688

    PubMed Central  PubMed  CAS  Google Scholar 

  • Ji RR, Samad TA, Jin SX, Schmoll R, Woolf CJ (2002) p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 36(1):57–68

    PubMed  CAS  Google Scholar 

  • Jin X, Morsy N, Winston J, Pasricha PJ, Garrett K, Akbarali HI (2004) Modulation of TRPV1 by nonreceptor tyrosine kinase, c-Src kinase. Am J Physiol Cell Physiol 287(2):C558–C563

    PubMed  CAS  Google Scholar 

  • Jordt SE, Julius D (2002) Molecular basis for species-specific sensitivity to “hot” chili peppers. Cell 108(3):421–430

    PubMed  CAS  Google Scholar 

  • Jordt SE, Tominaga M, Julius D (2000) Acid potentiation of the capsaicin receptor determined by a key extracellular site. Proc Natl Acad Sci USA 97(14):8134–8139

    PubMed Central  PubMed  CAS  Google Scholar 

  • Jung J, Lee SY, Hwang SW, Cho H, Shin J, Kang YS et al (2002) Agonist recognition sites in the cytosolic tails of vanilloid receptor 1. J Biol Chem 277(46):44448–44454

    PubMed  CAS  Google Scholar 

  • Jung J, Shin JS, Lee SY, Hwang SW, Koo J, Cho H et al (2004) Phosphorylation of vanilloid receptor 1 by Ca2+/calmodulin-dependent kinase II regulates its vanilloid binding. J Biol Chem 279(8):7048–7054

    PubMed  CAS  Google Scholar 

  • Kark T, Bagi Z, Lizanecz E, Pasztor ET, Erdei N, Czikora A et al (2008) Tissue-specific regulation of microvascular diameter: opposite functional roles of neuronal and smooth muscle located vanilloid receptor-1. Mol Pharmacol 73(5):1405–1412

    PubMed  CAS  Google Scholar 

  • Kawasaki H, Takasaki K, Saito A, Goto K (1988) Calcitonin gene-related peptide acts as a novel vasodilator neurotransmitter in mesenteric resistance vessels of the rat. Nature 335(6186):164–167

    PubMed  CAS  Google Scholar 

  • Kim H, Neubert JK, San Miguel A, Xu K, Krishnaraju RK, Iadarola MJ et al (2004) Genetic influence on variability in human acute experimental pain sensitivity associated with gender, ethnicity and psychological temperament. Pain 109(3):488–496

    PubMed  Google Scholar 

  • Kim AY, Tang Z, Liu Q, Patel KN, Maag D, Geng Y et al (2008) Pirt, a phosphoinositide-binding protein, functions as a regulatory subunit of TRPV1. Cell 133(3):475–485

    PubMed Central  PubMed  CAS  Google Scholar 

  • Kim SE, Patapoutian A, Grandl J (2013) Single residues in the outer pore of TRPV1 and TRPV3 have temperature-dependent conformations. PLoS One 8(3):e59593

    PubMed Central  PubMed  CAS  Google Scholar 

  • Kissin I, Szallasi A (2011) Therapeutic targeting of TRPV1 by resiniferatoxin, from preclinical studies to clinical trials. Curr Top Med Chem 11(17):2159–2170

    PubMed  CAS  Google Scholar 

  • Kitagawa Y, Tamai I, Hamada Y, Usui K, Wada M, Sakata M et al (2013a) The orally administered selective TRPV1 antagonist, JTS-653, attenuates chronic pain refractory to non-steroidal anti-inflammatory drugs in rats and mice including post-herpetic pain. J Pharmacol Sci 122(2):128–137

    PubMed  CAS  Google Scholar 

  • Kitagawa Y, Wada M, Kanehisa T, Miyai A, Usui K, Maekawa M et al (2013b) JTS-653 blocks afferent nerve firing and attenuates bladder overactivity without affecting normal voiding function. J Urol 189(3):1137–1146

    PubMed  CAS  Google Scholar 

  • Kiyatkin ME, Feng B, Schwartz ES, Gebhart GF (2013) Combined genetic and pharmacologic inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization. Am J Physiol Gastrointest Liver Physiol 305(9):G638–G648

    PubMed  CAS  Google Scholar 

  • Klein RM, Ufret-Vincenty CA, Hua L, Gordon SE (2008) Determinants of molecular specificity in phosphoinositide regulation. Phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2) is the endogenous lipid regulating TRPV1. J Biol Chem 283(38):26208–26216

    PubMed Central  PubMed  CAS  Google Scholar 

  • Koplas PA, Rosenberg RL, Oxford GS (1997) The role of calcium in the desensitization of capsaicin responses in rat dorsal root ganglion neurons. J Neurosci 17(10):3525–3537

    PubMed  CAS  Google Scholar 

  • Kort ME, Kym PR (2012) TRPV1 antagonists: clinical setbacks and prospects for future development. Prog Med Chem 51:57–70

    PubMed  CAS  Google Scholar 

  • Krarup AL, Ny L, Gunnarsson J, Hvid-Jensen F, Zetterstrand S, Simren M et al (2013) Randomized clinical trial: inhibition of the TRPV1 system in patients with nonerosive gastroesophageal reflux disease and a partial response to PPI treatment is not associated with analgesia to esophageal experimental pain. Scand J Gastroenterol 48(3):274–284

    PubMed  CAS  Google Scholar 

  • Lainez S, Valente P, Ontoria-Oviedo I, Estevez-Herrera J, Camprubi-Robles M, Ferrer-Montiel A et al (2010) GABAA receptor associated protein (GABARAP) modulates TRPV1 expression and channel function and desensitization. FASEB J 24(6):1958–1970

    PubMed  CAS  Google Scholar 

  • Lalloo UG, Fox AJ, Belvisi MG, Chung KF, Barnes PJ (1995) Capsazepine inhibits cough induced by capsaicin and citric acid but not by hypertonic saline in guinea pigs. J Appl Physiol 79(4):1082–1087

    PubMed  CAS  Google Scholar 

  • Latorre R, Brauchi S, Orta G, Zaelzer C, Vargas G (2007) ThermoTRP channels as modular proteins with allosteric gating. Cell Calcium 42(4–5):427–438

    PubMed  CAS  Google Scholar 

  • Latorre R, Zaelzer C, Brauchi S (2009) Structure-functional intimacies of transient receptor potential channels. Q Rev Biophys 42(3):201–246

    PubMed  CAS  Google Scholar 

  • Lau SY, Procko E, Gaudet R (2012) Distinct properties of Ca2 + -calmodulin binding to N- and C-terminal regulatory regions of the TRPV1 channel. J Gen Physiol 140(5):541–555

    PubMed Central  PubMed  CAS  Google Scholar 

  • Laude EA, Higgins KS, Morice AH (1993) A comparative study of the effects of citric acid, capsaicin and resiniferatoxin on the cough challenge in guinea-pig and man. Pulm Pharmacol 6(3):171–175

    PubMed  CAS  Google Scholar 

  • Lehto SG, Tamir R, Deng H, Klionsky L, Kuang R, Le A et al (2008) Antihyperalgesic effects of (R, E)-N-(2-hydroxy-2,3-dihydro-1H-inden-4-yl)-3-(2-(piperidin-1-yl)-4-(trifluorom ethyl)phenyl)-acrylamide (AMG8562), a novel transient receptor potential vanilloid type 1 modulator that does not cause hyperthermia in rats. J Pharmacol Exp Ther 326(1):218–229

    PubMed  CAS  Google Scholar 

  • Liao M, Cao E, Julius D, Cheng Y (2013) Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 504(7478):107–112

    PubMed  CAS  Google Scholar 

  • Lishko PV, Procko E, Jin X, Phelps CB, Gaudet R (2007) The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity. Neuron 54(6):905–918

    PubMed  CAS  Google Scholar 

  • Liu B, Hui K, Qin F (2003) Thermodynamics of heat activation of single capsaicin ion channels VR1. Biophys J 85(5):2988–3006

    PubMed Central  PubMed  CAS  Google Scholar 

  • Liu B, Ma W, Ryu S, Qin F (2004) Inhibitory modulation of distal C-terminal on protein kinase C-dependent phospho-regulation of rat TRPV1 receptors. J Physiol 560(Pt 3):627–638

    PubMed Central  PubMed  CAS  Google Scholar 

  • Liu B, Yao J, Wang Y, Li H, Qin F (2009) Proton inhibition of unitary currents of vanilloid receptors. J Gen Physiol 134(3):243–258

    PubMed Central  PubMed  CAS  Google Scholar 

  • Lukacs V, Thyagarajan B, Varnai P, Balla A, Balla T, Rohacs T (2007) Dual regulation of TRPV1 by phosphoinositides. J Neurosci 27(26):7070–7080

    PubMed  CAS  Google Scholar 

  • Lukacs V, Rives JM, Sun X, Zakharian E, Rohacs T (2013a) Promiscuous activation of transient receptor potential vanilloid 1 channels by negatively charged intracellular lipids, the key role of endogenous phosphoinositides in maintaining channel activity. J Biol Chem 288(49):35003–35013

    PubMed  CAS  Google Scholar 

  • Lukacs V, Yudin Y, Hammond GR, Sharma E, Fukami K, Rohacs T (2013b) Distinctive changes in plasma membrane phosphoinositides underlie differential regulation of TRPV1 in nociceptive neurons. J Neurosci 33(28):11451–11463

    PubMed Central  PubMed  CAS  Google Scholar 

  • Lyall V, Heck GL, Vinnikova AK, Ghosh S, Phan TH, Alam RI et al (2004) The mammalian amiloride-insensitive non-specific salt taste receptor is a vanilloid receptor-1 variant. J Physiol 558(Pt 1):147–159

    PubMed Central  PubMed  CAS  Google Scholar 

  • Malin SA, Molliver DC, Koerber HR, Cornuet P, Frye R, Albers KM et al (2006) Glial cell line-derived neurotrophic factor family members sensitize nociceptors in vitro and produce thermal hyperalgesia in vivo. J Neurosci 26(33):8588–8599

    PubMed  CAS  Google Scholar 

  • Mandadi S, Numazaki M, Tominaga M, Bhat MB, Armati PJ, Roufogalis BD (2004) Activation of protein kinase C reverses capsaicin-induced calcium-dependent desensitization of TRPV1 ion channels. Cell Calcium 35(5):471–478

    PubMed  CAS  Google Scholar 

  • Mandadi S, Tominaga T, Numazaki M, Murayama N, Saito N, Armati PJ et al (2006) Increased sensitivity of desensitized TRPV1 by PMA occurs through PKC epsilon-mediated phosphorylation at S800. Pain 123(1–2):106–116

    PubMed  CAS  Google Scholar 

  • Matta JA, Ahern GP (2007) Voltage is a partial activator of rat thermosensitive TRP channels. J Physiol 585(Pt 2):469–482

    PubMed Central  PubMed  CAS  Google Scholar 

  • McIntyre P, McLatchie LM, Chambers A, Phillips E, Clarke M, Savidge J et al (2001) Pharmacological differences between the human and rat vanilloid receptor 1 (VR1). Br J Pharmacol 132(5):1084–1094

    PubMed Central  PubMed  CAS  Google Scholar 

  • McLatchie LM, Bevan S (2001) The effects of pH on the interaction between capsaicin and the vanilloid receptor in rat dorsal root ganglia neurons. Br J Pharmacol 132(4):899–908

    PubMed Central  PubMed  CAS  Google Scholar 

  • Mezey E, Toth ZE, Cortright DN, Arzubi MK, Krause JE, Elde R et al (2000) 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(7):3655–3660

    PubMed Central  PubMed  CAS  Google Scholar 

  • Mohapatra DP, Nau C (2003) Desensitization of capsaicin-activated currents in the vanilloid receptor TRPV1 is decreased by the cyclic AMP-dependent protein kinase pathway. J Biol Chem 278(50):50080–50090

    PubMed  CAS  Google Scholar 

  • Mohapatra DP, Nau C (2005) Regulation of Ca2 + -dependent desensitization in the vanilloid receptor TRPV1 by calcineurin and cAMP-dependent protein kinase. J Biol Chem 280(14):13424–13432

    PubMed  CAS  Google Scholar 

  • Moiseenkova-Bell VY, Stanciu LA, Serysheva II, Tobe BJ, Wensel TG (2008) Structure of TRPV1 channel revealed by electron cryomicroscopy. Proc Natl Acad Sci USA 105(21):7451–7455

    PubMed Central  PubMed  CAS  Google Scholar 

  • Morenilla-Palao C, Planells-Cases R, Garcia-Sanz N, Ferrer-Montiel A (2004) Regulated exocytosis contributes to protein kinase C potentiation of vanilloid receptor activity. J Biol Chem 279(24):25665–25672

    PubMed  CAS  Google Scholar 

  • Morgan A, Burgoyne RD, Barclay JW, Craig TJ, Prescott GR, Ciufo LF et al (2005) Regulation of exocytosis by protein kinase C. Biochem Soc Trans 33(Pt 6):1341–1344

    PubMed  CAS  Google Scholar 

  • Myers BR, Bohlen CJ, Julius D (2008) A yeast genetic screen reveals a critical role for the pore helix domain in TRP channel gating. Neuron 58(3):362–373

    PubMed Central  PubMed  CAS  Google Scholar 

  • Myrdal SE, Steyger PS (2005) TRPV1 regulators mediate gentamicin penetration of cultured kidney cells. Hear Res 204(1–2):170–182

    PubMed Central  PubMed  CAS  Google Scholar 

  • Nagy I, Rang HP (1999) Similarities and differences between the responses of rat sensory neurons to noxious heat and capsaicin. J Neurosci 19(24):10647–10655

    PubMed  CAS  Google Scholar 

  • Nilius B, Appendino G (2013) Spices: the savory and beneficial science of pungency. Rev Physiol Biochem Pharmacol 164:1–76

    PubMed  Google Scholar 

  • Nilius B, Talavera K, Owsianik G, Prenen J, Droogmans G, Voets T (2005) Gating of TRP channels: a voltage connection? J Physiol 567(Pt 1):35–44

    PubMed Central  PubMed  CAS  Google Scholar 

  • Novakova-Tousova K, Vyklicky L, Susankova K, Benedikt J, Samad A, Teisinger J et al (2007) Functional changes in the vanilloid receptor subtype 1 channel during and after acute desensitization. Neuroscience 149(1):144–154

    PubMed  CAS  Google Scholar 

  • Numazaki M, Tominaga T, Toyooka H, Tominaga M (2002) Direct phosphorylation of capsaicin receptor VR1 by protein kinase C epsilon and identification of two target serine residues. J Biol Chem 277(16):13375–13378

    PubMed  CAS  Google Scholar 

  • Numazaki M, Tominaga T, Takeuchi K, Murayama N, Toyooka H, Tominaga M (2003) Structural determinant of TRPV1 desensitization interacts with calmodulin. Proc Natl Acad Sci USA 100(13):8002–8006

    PubMed Central  PubMed  CAS  Google Scholar 

  • Oh U, Hwang SW, Kim D (1996) Capsaicin activates a nonselective cation channel in cultured neonatal rat dorsal root ganglion neurons. J Neurosci 16(5):1659–1667

    PubMed  CAS  Google Scholar 

  • Owsianik G, Talavera K, Voets T, Nilius B (2006) Permeation and selectivity of TRP channels. Annu Rev Physiol 68:685–717

    PubMed  CAS  Google Scholar 

  • Pareek TK, Keller J, Kesavapany S, Agarwal N, Kuner R, Pant HC et al (2007) Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential vanilloid 1. Proc Natl Acad Sci USA 104(2):660–665

    PubMed Central  PubMed  CAS  Google Scholar 

  • Patwardhan AM, Jeske NA, Price TJ, Gamper N, Akopian AN, Hargreaves KM (2006) The cannabinoid WIN 55,212-2 inhibits transient receptor potential vanilloid 1 (TRPV1) and evokes peripheral antihyperalgesia via calcineurin. Proc Natl Acad Sci USA 103(30):11393–11398

    PubMed Central  PubMed  CAS  Google Scholar 

  • Patwardhan AM, Akopian AN, Ruparel NB, Diogenes A, Weintraub ST, Uhlson C et al (2010) Heat generates oxidized linoleic acid metabolites that activate TRPV1 and produce pain in rodents. J Clin Invest 120(5):1617–1626

    PubMed Central  PubMed  CAS  Google Scholar 

  • Phillips E, Reeve A, Bevan S, McIntyre P (2004) Identification of species-specific determinants of the action of the antagonist capsazepine and the agonist PPAHV on TRPV1. J Biol Chem 279(17):17165–17172

    PubMed  CAS  Google Scholar 

  • Piper AS, Yeats JC, Bevan S, Docherty RJ (1999) A study of the voltage dependence of capsaicin-activated membrane currents in rat sensory neurones before and after acute desensitization. J Physiol 518(Pt 3):721–733

    PubMed Central  PubMed  CAS  Google Scholar 

  • Por ED, Samelson BK, Belugin S, Akopian AN, Scott JD, Jeske NA (2010) PP2B/calcineurin-mediated desensitization of TRPV1 does not require AKAP150. Biochem J 432(3):549–556

    PubMed Central  PubMed  CAS  Google Scholar 

  • Premkumar LS, Agarwal S, Steffen D (2002) Single-channel properties of native and cloned rat vanilloid receptors. J Physiol 545(Pt 1):107–117

    PubMed Central  PubMed  CAS  Google Scholar 

  • Prescott ED, Julius D (2003) A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity. Science 300(5623):1284–1288

    PubMed  CAS  Google Scholar 

  • Puopolo M, Binshtok AM, Yao GL, Oh SB, Woolf CJ, Bean BP (2013) Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314. J Neurophysiol 109(7):1704–1712

    PubMed Central  PubMed  CAS  Google Scholar 

  • Rathee PK, Distler C, Obreja O, Neuhuber W, Wang GK, Wang SY et al (2002) PKA/AKAP/VR-1 module: a common link of Gs-mediated signaling to thermal hyperalgesia. J Neurosci 22(11):4740–4745

    PubMed  CAS  Google Scholar 

  • Reilly RM, McDonald HA, Puttfarcken PS, Joshi SK, Lewis L, Pai M et al (2012) Pharmacology of modality-specific transient receptor potential vanilloid-1 antagonists that do not alter body temperature. J Pharmacol Exp Ther 342(2):416–428

    PubMed  CAS  Google Scholar 

  • Roberts JC, Davis JB, Benham CD (2004) [3H]Resiniferatoxin autoradiography in the CNS of wild-type and TRPV1 null mice defines TRPV1 (VR-1) protein distribution. Brain Res 995(2):176–183

    PubMed  CAS  Google Scholar 

  • Rohacs T (2013) Regulation of transient receptor potential channels by the phospholipase C pathway. Adv Biol Regul 53(3):341–355

    PubMed  CAS  Google Scholar 

  • Romanovsky AA, Almeida MC, Garami A, Steiner AA, Norman MH, Morrison SF et al (2009) The transient receptor potential vanilloid-1 channel in thermoregulation: a thermosensor it is not. Pharmacol Rev 61(3):228–261

    PubMed Central  PubMed  CAS  Google Scholar 

  • Rosenbaum T, Gordon-Shaag A, Munari M, Gordon SE (2004) Ca2+/calmodulin modulates TRPV1 activation by capsaicin. J Gen Physiol 123(1):53–62

    PubMed Central  PubMed  CAS  Google Scholar 

  • Rowbotham MC, Nothaft W, Duan WR, Wang Y, Faltynek C, McGaraughty S et al (2011) Oral and cutaneous thermosensory profile of selective TRPV1 inhibition by ABT-102 in a randomized healthy volunteer trial. Pain 152(5):1192–1200

    PubMed  CAS  Google Scholar 

  • Ryu S, Liu B, Qin F (2003) Low pH potentiates both capsaicin binding and channel gating of VR1 receptors. J Gen Physiol 122(1):45–61

    PubMed Central  PubMed  CAS  Google Scholar 

  • Ryu S, Liu B, Yao J, Fu Q, Qin F (2007) Uncoupling proton activation of vanilloid receptor TRPV1. J Neurosci 27(47):12797–12807

    PubMed  CAS  Google Scholar 

  • Salazar H, Jara-Oseguera A, Hernandez-Garcia E, Llorente I, Arias O II, Soriano-Garcia M et al (2009) Structural determinants of gating in the TRPV1 channel. Nat Struct Mol Biol 16(7):704–710

    PubMed  CAS  Google Scholar 

  • Samways DS, Egan TM (2011) Calcium-dependent decrease in the single-channel conductance of TRPV1. Pflugers Arch 462(5):681–691

    PubMed Central  PubMed  CAS  Google Scholar 

  • Schnizler K, Shutov LP, Van Kanegan MJ, Merrill MA, Nichols B, McKnight GS et al (2008) Protein kinase A anchoring via AKAP150 is essential for TRPV1 modulation by forskolin and prostaglandin E2 in mouse sensory neurons. J Neurosci 28(19):4904–4917

    PubMed Central  PubMed  CAS  Google Scholar 

  • Sharif Naeini R, Witty MF, Seguela P, Bourque CW (2006) An N-terminal variant of Trpv1 channel is required for osmosensory transduction. Nat Neurosci 9(1):93–98

    PubMed  Google Scholar 

  • Shu X, Mendell LM (1999) Nerve growth factor acutely sensitizes the response of adult rat sensory neurons to capsaicin. Neurosci Lett 274(3):159–162

    PubMed  CAS  Google Scholar 

  • Siemens J, Zhou S, Piskorowski R, Nikai T, Lumpkin EA, Basbaum AI et al (2006) Spider toxins activate the capsaicin receptor to produce inflammatory pain. Nature 444(7116):208–212

    PubMed  CAS  Google Scholar 

  • Southall MD, Li T, Gharibova LS, Pei Y, Nicol GD, Travers JB (2003) Activation of epidermal vanilloid receptor-1 induces release of proinflammatory mediators in human keratinocytes. J Pharmacol Exp Ther 304(1):217–222

    PubMed  CAS  Google Scholar 

  • Staruschenko A, Jeske NA, Akopian AN (2010) Contribution of TRPV1-TRPA1 interaction to the single channel properties of the TRPA1 channel. J Biol Chem 285(20):15167–15177

    PubMed Central  PubMed  CAS  Google Scholar 

  • Steenland HW, Ko SW, Wu LJ, Zhuo M (2006) Hot receptors in the brain. Mol Pain 2:34

    PubMed Central  PubMed  Google Scholar 

  • Stein AT, Ufret-Vincenty CA, Hua L, Santana LF, Gordon SE (2006) Phosphoinositide 3-kinase binds to TRPV1 and mediates NGF-stimulated TRPV1 trafficking to the plasma membrane. J Gen Physiol 128(5):509–522

    PubMed Central  PubMed  CAS  Google Scholar 

  • Steiner AA, Turek VF, Almeida MC, Burmeister JJ, Oliveira DL, Roberts JL et al (2007) Nonthermal activation of transient receptor potential vanilloid-1 channels in abdominal viscera tonically inhibits autonomic cold-defense effectors. J Neurosci 27(28):7459–7468

    PubMed  CAS  Google Scholar 

  • Studer M, McNaughton PA (2010) Modulation of single-channel properties of TRPV1 by phosphorylation. J Physiol 588(Pt 19):3743–3756

    PubMed Central  PubMed  CAS  Google Scholar 

  • Sudbury JR, Ciura S, Sharif-Naeini R, Bourque CW (2010) Osmotic and thermal control of magnocellular neurosecretory neurons–role of an N-terminal variant of trpv1. Eur J Neurosci 32(12):2022–2030

    PubMed  Google Scholar 

  • Sugiura T, Tominaga M, Katsuya H, Mizumura K (2002) Bradykinin lowers the threshold temperature for heat activation of vanilloid receptor 1. J Neurophysiol 88(1):544–548

    PubMed  CAS  Google Scholar 

  • Suzuki M, Sato J, Kutsuwada K, Ooki G, Imai M (1999) Cloning of a stretch-inhibitable nonselective cation channel. J Biol Chem 274(10):6330–6335

    PubMed  CAS  Google Scholar 

  • Szallasi A, Blumberg PM (1999) Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev 51(2):159–212

    PubMed  CAS  Google Scholar 

  • Szolcsanyi J (1977) A pharmacological approach to elucidation of the role of different nerve fibres and receptor endings in mediation of pain. J Physiol Paris 73(3):251–259

    PubMed  CAS  Google Scholar 

  • Szolcsanyi J, Joo F, Jancso-Gabor A (1971) Mitochondrial changes in preoptic neurons after capsaicin desensitization of the hypothalamic thermodetectors in rats. Nature 229(5280):116–117

    PubMed  CAS  Google Scholar 

  • Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K et al (1998) The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21(3):531–543

    PubMed  CAS  Google Scholar 

  • Toth DM, Szoke E, Bolcskei K, Kvell K, Bender B, Bosze Z et al (2011) Nociception, neurogenic inflammation and thermoregulation in TRPV1 knockdown transgenic mice. Cell Mol Life Sci 68(15):2589–2601

    PubMed  CAS  Google Scholar 

  • Treesukosol Y, Lyall V, Heck GL, DeSimone JA, Spector AC (2007) A psychophysical and electrophysiological analysis of salt taste in Trpv1 null mice. Am J Physiol Regul Integr Comp Physiol 292(5):R1799–R1809

    PubMed  CAS  Google Scholar 

  • Ufret-Vincenty CA, Klein RM, Hua L, Angueyra J, Gordon SE (2011) Localization of the PIP2 sensor of TRPV1 ion channels. J Biol Chem 286(11):9688–9698

    PubMed Central  PubMed  CAS  Google Scholar 

  • Urban L, Campbell EA, Panesar M, Patel S, Chaudhry N, Kane S et al (2000) In vivo pharmacology of SDZ 249-665, a novel, non-pungent capsaicin analogue. Pain 89(1):65–74

    PubMed  CAS  Google Scholar 

  • Ursu D, Knopp K, Beattie RE, Liu B, Sher E (2010) Pungency of TRPV1 agonists is directly correlated with kinetics of receptor activation and lipophilicity. Eur J Pharmacol 641(2–3):114–122

    PubMed  CAS  Google Scholar 

  • Valente P, Garcia-Sanz N, Gomis A, Fernandez-Carvajal A, Fernandez-Ballester G, Viana F et al (2008) Identification of molecular determinants of channel gating in the transient receptor potential box of vanilloid receptor I. FASEB J 22(9):3298–3309

    PubMed  CAS  Google Scholar 

  • Vellani V, Mapplebeck S, Moriondo A, Davis JB, McNaughton PA (2001) Protein kinase C activation potentiates gating of the vanilloid receptor VR1 by capsaicin, protons, heat and anandamide. J Physiol 534(Pt 3):813–825

    PubMed Central  PubMed  CAS  Google Scholar 

  • Vellani V, Kinsey AM, Prandini M, Hechtfischer SC, Reeh P, Magherini PC et al (2010) Protease activated receptors 1 and 4 sensitize TRPV1 in nociceptive neurones. Mol Pain 6:61

    PubMed Central  PubMed  Google Scholar 

  • Venkatachalam K, Montell C (2007) TRP channels. Annu Rev Biochem 76:387–417

    PubMed  CAS  Google Scholar 

  • Virginio C, MacKenzie A, Rassendren FA, North RA, Surprenant A (1999) Pore dilation of neuronal P2X receptor channels. Nat Neurosci 2(4):315–321

    PubMed  CAS  Google Scholar 

  • Vlachova V, Teisinger J, Susankova K, Lyfenko A, Ettrich R, Vyklicky L (2003) Functional role of C-terminal cytoplasmic tail of rat vanilloid receptor 1. J Neurosci 23(4):1340–1350

    PubMed  CAS  Google Scholar 

  • Voets T (2012) Quantifying and modeling the temperature-dependent gating of TRP channels. Rev Physiol Biochem Pharmacol 162:91–119

    PubMed  CAS  Google Scholar 

  • Voets T (2014) TRP channels and thermosensation. In: Nilius B, Flockerzi V (eds) Mammalian transient receptor potential (TRP) cation channels. Springer, Heidelberg

    Google Scholar 

  • Voets T, Droogmans G, Wissenbach U, Janssens A, Flockerzi V, Nilius B (2004) The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels. Nature 430(7001):748–754

    PubMed  CAS  Google Scholar 

  • Voets T, Owsianik G, Janssens A, Talavera K, Nilius B (2007) TRPM8 voltage sensor mutants reveal a mechanism for integrating thermal and chemical stimuli. Nat Chem Biol 3(3):174–182

    PubMed  CAS  Google Scholar 

  • Vos MH, Neelands TR, McDonald HA, Choi W, Kroeger PE, Puttfarcken PS et al (2006) TRPV1b overexpression negatively regulates TRPV1 responsiveness to capsaicin, heat and low pH in HEK293 cells. J Neurochem 99(4):1088–1102

    PubMed  CAS  Google Scholar 

  • Vyklicky L, Vlachova V, Vitaskova Z, Dittert I, Kabat M, Orkand RK (1999) Temperature coefficient of membrane currents induced by noxious heat in sensory neurones in the rat. J Physiol 517(Pt 1):181–192

    PubMed Central  PubMed  CAS  Google Scholar 

  • Walker KM, Urban L, Medhurst SJ, Patel S, Panesar M, Fox AJ et al (2003) The VR1 antagonist capsazepine reverses mechanical hyperalgesia in models of inflammatory and neuropathic pain. J Pharmacol Exp Ther 304(1):56–62

    PubMed  CAS  Google Scholar 

  • Wang S, Poon K, Oswald RE, Chuang HH (2010) Distinct modulations of human capsaicin receptor by protons and magnesium through different domains. J Biol Chem 285(15):11547–11556

    PubMed Central  PubMed  CAS  Google Scholar 

  • Welch JM, Simon SA, Reinhart PH (2000) The activation mechanism of rat vanilloid receptor 1 by capsaicin involves the pore domain and differs from the activation by either acid or heat. Proc Natl Acad Sci USA 97(25):13889–13894

    PubMed Central  PubMed  CAS  Google Scholar 

  • Winter J, Forbes CA, Sternberg J, Lindsay RM (1988) Nerve growth factor (NGF) regulates adult rat cultured dorsal root ganglion neuron responses to the excitotoxin capsaicin. Neuron 1(10):973–981

    PubMed  CAS  Google Scholar 

  • Winter J, Dray A, Wood JN, Yeats JC, Bevan S (1990) Cellular mechanism of action of resiniferatoxin: a potent sensory neuron excitotoxin. Brain Res 520(1–2):131–140

    PubMed  CAS  Google Scholar 

  • Wiskur BJ, Tyler K, Campbell-Dittmeyer K, Chaplan SR, Wickenden AD, Greenwood-Van MB (2010) A novel TRPV1 receptor antagonist JNJ-17203212 attenuates colonic hypersensitivity in rats. Methods Find Exp Clin Pharmacol 32(8):557–564

    PubMed  CAS  Google Scholar 

  • Woodbury CJ, Zwick M, Wang S, Lawson JJ, Caterina MJ, Koltzenburg M et al (2004) Nociceptors lacking TRPV1 and TRPV2 have normal heat responses. J Neurosci 24(28):6410–6415

    PubMed  CAS  Google Scholar 

  • Xing BM, Yang YR, Du JX, Chen HJ, Qi C, Huang ZH et al (2012) Cyclin-dependent kinase 5 controls TRPV1 membrane trafficking and the heat sensitivity of nociceptors through KIF13B. J Neurosci 32(42):14709–14721

    PubMed  CAS  Google Scholar 

  • Xu H, Tian W, Fu Y, Oyama TT, Anderson S, Cohen DM (2007) Functional effects of nonsynonymous polymorphisms in the human TRPV1 gene. Am J Physiol Renal Physiol 293(6):F1865–F1876

    PubMed  CAS  Google Scholar 

  • Xue Q, Yu Y, Trilk SL, Jong BE, Schumacher MA (2001) The genomic organization of the gene encoding the vanilloid receptor: evidence for multiple splice variants. Genomics 76(1–3):14–20

    PubMed  CAS  Google Scholar 

  • Yamada T, Ugawa S, Ueda T, Ishida Y, Kajita K, Shimada S (2009) Differential localizations of the transient receptor potential channels TRPV4 and TRPV1 in the mouse urinary bladder. J Histochem Cytochem 57(3):277–287

    PubMed Central  PubMed  CAS  Google Scholar 

  • Yang F, Cui Y, Wang K, Zheng J (2010) Thermosensitive TRP channel pore turret is part of the temperature activation pathway. Proc Natl Acad Sci USA 107(15):7083–7088

    PubMed Central  PubMed  CAS  Google Scholar 

  • Yao J, Qin F (2009) Interaction with phosphoinositides confers adaptation onto the TRPV1 pain receptor. PLoS Biol 7(2):e46

    PubMed  Google Scholar 

  • Yao J, Liu B, Qin F (2010) Kinetic and energetic analysis of thermally activated TRPV1 channels. Biophys J 99(6):1743–1753

    PubMed Central  PubMed  CAS  Google Scholar 

  • Yao J, Liu B, Qin F (2011) Modular thermal sensors in temperature-gated transient receptor potential (TRP) channels. Proc Natl Acad Sci USA 108(27):11109–11114

    PubMed Central  PubMed  CAS  Google Scholar 

  • Yu FH, Catterall WA (2004) The VGL-chanome: a protein superfamily specialized for electrical signaling and ionic homeostasis. Sci STKE 2004(253):re15

    PubMed  Google Scholar 

  • Zakharian E, Cao C, Rohacs T (2010) Gating of transient receptor potential melastatin 8 (TRPM8) channels activated by cold and chemical agonists in planar lipid bilayers. J Neurosci 30(37):12526–12534

    PubMed Central  PubMed  CAS  Google Scholar 

  • Zeilhofer HU, Kress M, Swandulla D (1997) Fractional Ca2+ currents through capsaicin- and proton-activated ion channels in rat dorsal root ganglion neurones. J Physiol 503(Pt 1):67–78

    PubMed Central  PubMed  CAS  Google Scholar 

  • Zhang X, Huang J, McNaughton PA (2005) NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. EMBO J 24(24):4211–4223

    PubMed Central  PubMed  CAS  Google Scholar 

  • Zhang X, Li L, McNaughton PA (2008) Proinflammatory mediators modulate the heat-activated ion channel TRPV1 via the scaffolding protein AKAP79/150. Neuron 59(3):450–461

    PubMed  Google Scholar 

  • Zhang X, Daugherty SL, de Groat WC (2011) Activation of CaMKII and ERK1/2 contributes to the time-dependent potentiation of Ca2+ response elicited by repeated application of capsaicin in rat DRG neurons. Am J Physiol Regul Integr Comp Physiol 300(3):R644–R654

    PubMed Central  PubMed  CAS  Google Scholar 

  • Zhu W, Oxford GS (2007) Phosphoinositide-3-kinase and mitogen activated protein kinase signaling pathways mediate acute NGF sensitization of TRPV1. Mol Cell Neurosci 34(4):689–700

    PubMed Central  PubMed  CAS  Google Scholar 

  • Zhuang ZY, Xu H, Clapham DE, Ji RR (2004) Phosphatidylinositol 3-kinase activates ERK in primary sensory neurons and mediates inflammatory heat hyperalgesia through TRPV1 sensitization. J Neurosci 24(38):8300–8309

    PubMed  CAS  Google Scholar 

  • Zygmunt PM, Petersson J, Andersson DA, Chuang H, Sorgard M, Di Marzo V et al (1999) Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400(6743):452–457

    PubMed  CAS  Google Scholar 

  • Zygmunt PM, Ermund A, Movahed P, Andersson DA, Simonsen C, Jonsson BA et al (2013) Monoacylglycerols activate TRPV1—a link between phospholipase C and TRPV1. PLoS One 8(12):e81618

    PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Wolfson Centre for Age Related Diseases, King’s College London, London, SE1 1UL, UK

    Stuart Bevan, Talisia Quallo & David A. Andersson

Authors
  1. Stuart Bevan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Talisia Quallo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David A. Andersson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stuart Bevan .

Editor information

Editors and Affiliations

  1. Laboratory Ion Channel Research Campus Gasthuisberg, KU Leuven Department Cell Mol Medicin, Leuven, Belgium

    Bernd Nilius

  2. Institut für Experimentelle u. Klinische, Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg, Saarland, Germany

    Veit Flockerzi

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Bevan, S., Quallo, T., Andersson, D.A. (2014). TRPV1. In: Nilius, B., Flockerzi, V. (eds) Mammalian Transient Receptor Potential (TRP) Cation Channels. Handbook of Experimental Pharmacology, vol 222. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-54215-2_9

Download citation

Publish with us

Policies and ethics

Search

Navigation