Abstract
The TRPV1 channel is a polymodal receptor that has been implicated in several physiological and pathological processes including painful stimuli detection, inflammation, hyperalgesia and, recently, mechanotransduction. This channel can be directly activated by acidic pH, bioactive lipids, cysteine-modifying molecules, extracellular cations, voltage, elevated temperatures and several exogenous molecules such as capsaicin and toxins from animals. Moreover, its function can be modulated by the action of protein kinases, lipids, the cytoskeleton, second messengers and many proteins involved in signaling processes. Hence, the TRPV1 channel sits in the middle of the cell’s intracellular signaling network and its communication with the external environment. Understanding the molecular mechanisms that govern TRPV1 channel function will certainly allow us to obtain a deeper insight into the physiology of cells and organisms. Here we review the latest discoveries pertaining the mechanisms and signaling processes that affect TRPV1 activity.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReference
Ahern GP (2003) Activation of TRPV1 by the satiety factor oleoylethanolamide. J Biol Chem 278:30429–30434
Ahern GP, Brooks IM, Miyares RL, Wang XB (2005) Extracellular cations sensitize and gate capsaicin receptor TRPV1 modulating pain signaling. J Neurosci 25:5109–5116
Ahern GP, Wang X, Miyares RL (2006) Polyamines are potent ligands for the capsaicin receptor TRPV1. J Biol Chem 281:8991–8995
Amadesi S, Cottrell GS, Divino L, Chapman K, Grady EF, Bautista F, Karanjia R, Barajas-Lopez C, Vanner S, Vergnolle N, Bunnett NW (2006) Protease-activated receptor 2 sensitizes TRPV1 by protein kinase Cepsilon- and A-dependent mechanisms in rats and mice. J Physiol 575:555–571
Aneiros E, Cao L, Papakosta M, Stevens EB, Phillips S, Grimm C (2011) The biophysical and molecular basis of TRPV1 proton gating. EMBO J 30:994–1002
Artim DE, Bazely F, Daugherty SL, Sculptoreanu A, Koronowski KB, Schopfer FJ, Woodcock SR, Freeman BA, de Groat WC (2011) Nitro-oleic acid targets transient receptor potential (TRP) channels in capsaicin sensitive afferent nerves of rat urinary bladder. Exp Neurol 232:90–99
Avelino A, Cruz F (2006) TRPV1 (vanilloid receptor) in the urinary tract: expression, function and clinical applications. Naunyn Schmiedebergs Arch Pharmacol 373:287–299
Baumann TK, Martenson ME (2000) Extracellular protons both increase the activity and reduce the conductance of capsaicin- gated channels. J Neurosci 20:RC80
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
Bhave G, Hu HJ, Glauner KS, Zhu W, Wang H, Brasier DJ, Oxford GS, Gereau R Wt (2003) Protein kinase C phosphorylation sensitizes but does not activate the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1). Proc Natl Acad Sci U S A 100:12480–12485
Bhave G, Zhu W, Wang H, Brasier D, Oxford G, IV RG (2002) cAmp-Dependent protien kinase regulates desensitization of the capsaicin receptor (VR1) by direct phosphorylation. Neuron 35:721–731
Birder LA, Kanai AJ, de Groat WC, Kiss S, Nealen ML, Burke NE, Dineley KE, Watkins S, Reynolds IJ, Caterina MJ (2001) Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells. Proc Natl Acad Sci USA 98:13396–13401
Birder LA, Nakamura Y, Kiss S, Nealen ML, Barrick S, Kanai AJ, Wang E, Ruiz G, De Groat WC, Apodaca G, Watkins S, Caterina MJ (2002) Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat Neurosci 5:856–860
Bohlen C, 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 141:834–845
Boukalova S, Marsakova L, Teisinger J, Vlachova V (2010) Conserved residues within the putative S4–S5 region serve distinct functions among thermosensitive vanilloid transient receptor potential (TRPV) channels. J Biol Chem 285:41455–41462
Bourque CW (2008) Central mechanisms of osmosensation and systemic osmoregulation. Nat Rev Neurosci 9:519–531
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 101:15494–15499
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 26:4835–4840
Brauchi S, Orta G, Mascayano C, Salazar M, Raddatz N, Urbina H, Rosenmann E, Gonzalez-Nilo F, Latorre R (2007) Dissection of the components for PIP2 activation and thermosensation in TRP channels. Proc Natl Acad Sci USA 104:10246–10251
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 23:3722–3733
Cantero-Recasens G, Gonzalez JR, Fandos C, Duran-Tauleria E, Smit LA, Kauffmann F, Anto JM, Valverde MA (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 285:27532–27535
Caterina MJ, Julius D (2001) The vanilloid receptor: a molecular gateway to the pain pathway. Annu Rev Neurosci 24:487–517
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 389:816–824
Catterall WA (2010) Ion channel voltage sensors: structure, function, and pathophysiology. Neuron 67:915–928
Cesare P, McNaughton P (1996) A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin. Proc Natl Acad Sci USA 93:15435–15439
Cesare P, Dekker LV, Sardini A, Parker PJ, McNaughton PA (1999) Specific involvement of PKC-epsilon in sensitization of the neuronal response to painful heat. Neuron 23:617–624
Ciura S, Bourque C (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 26:9069–9075
Chakfe Y, Bourque CW (2000) Excitatory peptides and osmotic pressure modulate mechanosensitive cation channels in concert. Nat Neurosci 3:572–579
Chan CL, Facer P, Davis JB, Smith GD, Egerton J, Bountra C, Williams NS, Anand P (2003) Sensory fibres expressing capsaicin receptor TRPV1 in patients with rectal hypersensitivity and faecal urgency. Lancet 361:385–391
Chaudhury S, Bal M, Belugin S, Shapiro MS, Jeske NA (2011) AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin. Mol Pain 7:34
Chen YS, Lu MJ, Huang HS, Ma MC (2010) Mechanosensitive transient receptor potential vanilloid type 1 channels contribute to vascular remodeling of rat fistula veins. J Vasc Surg 52:1310–1320
Chou MZ, Mtui T, Gao YD, Kohler M, Middleton RE (2004) Resiniferatoxin binds to the capsaicin receptor (TRPV1) near the extracellular side of the S4 transmembrane domain. Biochemistry 43:2501–2511
Christoph T, Grunweller A, Mika J, Schafer MK, Wade EJ, Weihe E, Erdmann VA, Frank R, Gillen C, Kurreck J (2006) Silencing of vanilloid receptor TRPV1 by RNAi reduces neuropathic and visceral pain in vivo. Biochem Biophys Res Commun 350:238–243
Chu CJ, Huang SM, De Petrocellis L, Bisogno T, Ewing SA, Miller JD, Zipkin RE, Daddario N, Appendino G, Di Marzo V, Walker JM (2003) N-oleoyldopamine, a novel endogenous capsaicin-like lipid that produces hyperalgesia. J Biol Chem 278:13633–13639
Chuang HH, Lin S (2009) Oxidative challenges sensitize the capsaicin receptor by covalent cysteine modification. Proc Natl Acad Sci USA 106:20097–20102
Chuang HH, Prescott ED, Kong H, Shields S, Jordt SE, Basbaum AI, Chao MV, Julius D (2001) Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature 411:957–962
Chung MK, Guler AD, Caterina MJ (2008) TRPV1 shows dynamic ionic selectivity during agonist stimulation. Nat Neurosci 11:555–564
Daly D, Rong W, Chess-Williams R, Chapple C, Grundy D (2007) Bladder afferent sensitivity in wild-type and TRPV1 knockout mice. J Physiol 583:663–674
Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, Overend P, Harries MH, Latcham J, Clapham C, Atkinson K, Hughes SA, Rance K, Grau E, Harper A J, Pugh PL, Rogers DC, Bingham S, Randall A, Sheardown SA (2000) Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405:183–187
De Petrocellis L, Bisogno T, Davis JB, Pertwee RG, Di Marzo V (2000) Overlap between the ligand recognition properties of the anandamide transporter and the VR1 vanilloid receptor: inhibitors of anandamide uptake with negligible capsaicin-like activity. FEBS Lett 483:52–56
De Petrocellis L, Chu CJ, Moriello AS, Kellner JC, Walker JM, Di Marzo V (2004) Actions of two naturally occurring saturated N-acyldopamines on transient receptor potential vanilloid 1 (TRPV1) channels. Br J Pharmacol 143:251–256
De Petrocellis L, Davis JB, Di Marzo V (2001a) Palmitoylethanolamide enhances anandamide stimulation of human vanilloid VR1 receptors. FEBS Lett 506:253–256
De Petrocellis L, Harrison S, Bisogno T, Tognetto M, Brandi I, Smith GD, Creminon C, Davis JB, Geppetti P, Di Marzo V (2001b) The vanilloid receptor (VR1)-mediated effects of anandamide are potently enhanced by the cAMP-dependent protein kinase. J Neurochem 77:1660–1663
Dhaka A, Uzzell V, Dubin AE, Mathur J, Petrus M, Bandell M, Patapoutian A (2009) TRPV1 is activated by both acidic and basic pH. J Neurosci 29:153–158
Di Marzo V, Fontana A, Cadas H, Schinelli S, Cimino G, Schwartz JC, Piomelli D (1994) Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature 372:686–691
Di Marzo V, Blumberg PM, Szallasi A (2002) Endovanilloid signaling in pain. Curr Opin Neurobiol 12:372–379
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 431:828–837
Everaerts W, Vriens J, Owsianik G, Appendino G, Voets T, De Ridder D, Nilius B (2010) Functional characterization of transient receptor potential channels in mouse urothelial cells. Am J Physiol Renal Physiol 298:F692–701
Fernandez-Ballester G, Ferrer-Montiel A (2008) Molecular modeling of the full-length human TRPV1 channel in closed and desensitized states. J Membr Biol 223:161–172
Gamper N, Shapiro MS (2007) Regulation of ion transport proteins by membrane phosphoinositides. Nat Rev Neurosci 8:921–934
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 275:32552–32558
García-Sanz N, Fernández-Carvajal A, Morenilla-Palao C, Planells-Cases R, Fajardo-Sánchez E, Fernández-Ballester G, Ferrer-Montiel A (2004) Identification of a tetramerization domain in the C terminus of the Vanilloid receptor. J Neurosci 24:5307–5314
García-Sanz N, Valente P, Gomis A, Fernandez-Carvajal A, Fernandez-Ballester G, Viana F, Belmonte C, Ferrer-Montiel A (2007) A role of the transient receptor potential domain of vanilloid receptor I in channel gating. J Neurosci 27:11641–11650
Gaudet R (2008) A primer on ankyrin repeat function in Trp channels and beyond. Molecular BioSystems 4:372–379
Gavva NR, Klionsky L, Qu Y, Shi L, Tamir R, Edenson S, Zhang TJ, Viswanadhan V N, Toth A, Pearce LV, Vanderah TW, Porreca F, Blumberg PM, Lile J, Sun Y, Wild K, Louis JC, Treanor JJ (2004) Molecular determinants of vanilloid sensitivity in TRPV1. J Biol Chem 279:20283–20295
Goswami C, Dreger M, Jahnel R, Bogen O, Gillen C, Hucho F (2004) Identification and characterization of a Ca2+-sensitive interaction of the vanilloid receptor TRPV1 with tubulin. J Neurochem 91:1092–1103
Goswami C, Dreger M, Otto H, Schwappach B, Hucho F (2006) Rapid disassembly of dynamic microtubules upon activation of the capsaicin receptor TRPV1. J Neurochem 96:254–266
Goswami C, Hucho TB, Hucho F (2007a) Identification and characterisation of novel tubulin-binding motifs located within the C-terminus of TRPV1. J Neurochem 101:250–262
Goswami C, Schmidt H, Hucho F (2007b) TRPV1 at nerve endings regulates growth cone morphology and movement through cytoskeleton reorganization. Febs J 274:760–772
Goswami C, Kuhn J, Dina OA, Fernandez-Ballester G, Levine JD, Ferrer-Montiel A, Hucho T (2011) Estrogen destabilizes microtubules through an ion-conductivity-independent TRPV1 pathway. J Neurochem 117:995–1008
Gracheva EO, Cordero-Morales JF, Gonzalez-Carcacia JA, Ingolia NT, Manno C, Aranguren CI, Weissman JS, Julius D (2011) Ganglion-specific splicing of TRPV1 underlies infrared sensation in vampire bats. Nature 476:88–91
Grandl J, Kim S, Uzzell V, Bursulaya B, Petrus M, Bandell M, Patapoutian A (2010) Temperature-induced opening of TRPV1 ion channel is stabilized by the pore domain. Nat Neurosci
Guesnet P, Alessandri J M (2011) Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) – Implications for dietary recommendations. Biochimie 93:7–12
Gunthorpe MJ, Harries MH, Prinjha RK, Davis JB, Randall A (2000) Voltage- and time-dependent properties of the recombinant rat vanilloid receptor (rVR1). J Physiol 525 Pt 3:747–759
Hatae T, Kawano H, Karpitskiy V, Krause JE, Masuko S (2001) Arginine-vasopressin neurons in the rat hypothalamus produce neurokinin B and co-express the tachykinin NK-3 receptor and angiotensin II type 1 receptor. Arch Histol Cytol 64:37–44
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 279:34553–34561
Heng YJ, Saunders CI, Kunde DA, Geraghty DP (2011) TRPV1, NK1 receptor and substance P immunoreactivity and gene expression in the rat lumbosacral spinal cord and urinary bladder after systemic, low dose vanilloid administration. Regul Pept 167:250–258
Huang SM, Bisogno T, Trevisani M, Al-Hayani A, De Petrocellis L, Fezza F, Tognetto M, Petros TJ, Krey JF, Chu CJ, Miller JD, Davies SN, Geppetti P, Walker JM, Di Marzo V (2002) An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors. Proc Natl Acad Sci USA 99:8400–8405
Hwang SW, Cho H, Kwak J, Lee SY, Kang CJ, Jung J, Cho S, Min KH, Suh YG, Kim D, Oh U (2000) Direct activation of capsaicin receptors by products of lipoxygenases: endogenous capsaicin-like substances. Proc Natl Acad Sci USA 97:6155–6160
Iida T, Moriyama T, Kobata K, Morita A, Murayama N, Hashizume S, Fushiki T, Yazawa S, Watanabe T, Tominaga M (2003) TRPV1 activation and induction of nociceptive response by a non-pungent capsaicin-like compound, capsiate. Neuropharmacology 44:958–967
Inoue M, Rashid M, Fujita R, Contos J, Chun J, Ueda H (2004) Initiation of neuropathic pain requires lysophosphatidic acid receptor signaling. Nat Med 10(7):712–718
Inoue R, Jensen LJ, Jian Z, Shi J, Hai L, Lurie AI, Henriksen FH, Salomonsson M, Morita H, Kawarabayashi Y, Mori M, Mori Y, Ito Y (2009) Synergistic activation of vascular TRPC6 channel by receptor and mechanical stimulation via phospholipase C/diacylglycerol and phospholipase A2/omega-hydroxylase/20-HETE pathways. Circ Res 104:1399–1409
Islas LD, Salazar H, Jara-Oseguera A, Nieto-Posadas A, Llorente I, Rangel-Yescas G, Rosenbaum T (2009) The helical character of the S6 segment of TRPV1 channels. Channels (Austin) 3:311–313
Iwasaki Y, Morita A, Iwasawa T, Kobata K, Sekiwa Y, Morimitsu Y, Kubota K, Watanabe T (2006) A nonpungent component of steamed ginger–[10]-shogaol–increases adrenaline secretion via the activation of TRPV1. Nutr Neurosci 9:169–178
Iwasaki Y, Saito O, Tanabe M, Inayoshi K, Kobata K, Uno S, Morita A, Watanabe T (2008) Monoacylglycerols activate capsaicin receptor, TRPV1. Lipids 43:471–483
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 132:547–562
Jara-Oseguera A, Nieto-Posadas A, Szallasi A, Islas LD, Rosenbaum T (2010) Molecular Mechanisms of TRPV1 Channel Activation. The Open Pain Journal 3:68–81
Jeske NA, Patwardhan AM, Gamper N, Price TJ, Akopian AN, Hargreaves KM (2006) Cannabinoid WIN 55,212–2 regulates TRPV1 phosphorylation in sensory neurons. J Biol Chem 281:32879–32890
Jeske NA, Patwardhan AM, Henry MA, Milam SB (2009a) Fibronectin stimulates TRPV1 translocation in primary sensory neurons. J Neurochem 108:591–600
Jeske NA, Patwardhan AM, Ruparel NB, Akopian AN, Shapiro MS, Henry MA (2009b) A-kinase anchoring protein 150 controls protein kinase C-mediated phosphorylation and sensitization of TRPV1. Pain 146:301–307
Jin Y, Kim DK, Khil LY, Oh U, Kim J, Kwak J (2004) Thimerosal decreases TRPV1 activity by oxidation of extracellular sulfhydryl residues. Neurosci Lett 369:250–255
Jin X, Touhey J, Gaudet R (2006) Structure of the N-terminal ankyrin repeat domain of the TRPV2 ion channel. J Biol Chem 281(35):25006–25010
Jira W, Spiteller G, Richter A (1997) Increased levels of lipid oxidation products in low density lipoproteins of patients suffering from rheumatoid arthritis. Chem Phys Lipids 87:81–89
Jones RC, 3rd, Xu L, Gebhart GF (2005) The mechanosensitivity of mouse colon afferent fibers and their sensitization by inflammatory mediators require transient receptor potential vanilloid 1 and acid-sensing ion channel 3. J Neurosci 25:10981–10989
Jordt SE, Julius D (2002) Molecular basis for species-specific sensitivity to "hot" chili peppers. Cell 108:421–430
Jordt SE, Tominaga M, Julius D (2000) Acid potentiation of the capsaicin receptor determined by a key extracellular site. Proc Natl Acad Sci USA 97:8134–8139
Jung J, Hwang SW, Kwak J, Lee SY, Kang CJ, Kim WB, Kim D, Oh U (1999) Capsaicin binds to the intracellular domain of the capsaicin-activated ion channel. J Neurosci 19:529–538
Jung J, Lee SY, Hwang SW, Cho H, Shin J, Kang YS, Kim S, Oh U (2002) Agonist recognition sites in the cytosolic tails of vanilloid receptor 1. J Biol Chem 277:44448–44454
Jung J, Shin JS, Lee SY, Hwang SW, Koo J, Cho H, Oh U (2004) Phosphorylation of vanilloid receptor 1 by Ca2+/calmodulin-dependent kinase II regulates its vanilloid binding. J Biol Chem 279:7048–7054
Kedei N, Szabo T, Lile JD, Treanor JJ, Olah Z, Iadarola MJ, Blumberg PM (2001) Analysis of the native quaternary structure of vanilloid receptor 1. J Biol Chem 276:28613–28619
Khoo NK, Freeman BA (2011) Electrophilic nitro-fatty acids: anti-inflammatory mediators in the vascular compartment. Curr Opin Pharmacol 10:179–184
Kim A, Tang Z, Liu Q, Patel K, Maag D, Geng Y, Dong X (2008) Pirt, a phosphoinositide-binding protein, functions as a regulatory subunit of TRPV1. Cell 133(3):475–485
Klein R, Ufret-Vincenty C, Hua L, Gordon S (2008) Determinants of molecular specificity in phosphoinositide regulation. J Biol Chem 283:26208–26216
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 17:3525–3537
Kuzhikandathil EV, Wang H, Szabo T, Morozova N, Blumberg PM, Oxford GS (2001) Functional analysis of capsaicin receptor (vanilloid receptor subtype 1) multimerization and agonist responsiveness using a dominant negative mutation. J Neurosci 21:8697–8706
Kwak J, Wang MH, Hwang SW, Kim TY, Lee SY, Oh U (2000) Intracellular ATP increases capsaicin-activated channel activity by interacting with nucleotide-binding domains. J Neurosci 20:8298–8304
Laird JM, Martinez-Caro L, Garcia-Nicas E, Cervero F (2001) A new model of visceral pain and referred hyperalgesia in the mouse. Pain 92:335–342
Latorre R, Brauchi S, Orta G, Zaelzer C, Vargas G (2007) ThermoTRP channels as modular proteins with allosteric gating. Cell Calcium 42:427–438
Lee TH, Mencia-Huerta JM, Shih C, Corey EJ, Lewis RA, Austen KF (1984) Effects of exogenous arachidonic, eicosapentaenoic, and docosahexaenoic acids on the generation of 5-lipoxygenase pathway products by ionophore-activated human neutrophils. J Clin Invest 74:1922–1933
Levine JD, Taiwo YO (1990) Hyperalgesic pain: a review. Anesth Prog 37:133–135
Lilja J, Laulund F, Forsby A (2007) Insulin and insulin-like growth factor type-I up-regulate the vanilloid receptor-1 (TRPV1) in stably TRPV1-expressing SH-SY5Y neuroblastoma cells. J Neurosci Res 85:1413–1419
Lin ME, Herr DR, Chun J (2010) Lysophosphatidic acid (LPA) receptors: signaling properties and disease relevance. Prostaglandins Other Lipid Mediat 91:130–138
Lishko P, Procko E, Jin X, Phelps CRG (2007) The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity. Neuron 54:905–918
Liu L, Simon SA (1996) Capsaicin-induced currents with distinct desensitization and Ca2+dependence in rat trigeminal ganglion cells. J Neurophysiol 75:1503–1514
Liu B, Hui K, Qin F (2003) Thermodynamics of heat activation of single capsaicin ion channels VR1. Biophys J 85:2988–3006
Liu B, Zhang C, Qin F (2005) Functional recovery from desensitization of vanilloid receptor TRPV1 requires resynthesis of phosphatidylinositol 4,5-bisphosphate. J Neurosci 25:4835–4843
Liu M, Huang W, Wu D, Priestley JV (2006) TRPV1, but not P2X, requires cholesterol for its function and membrane expression in rat nociceptors. Eur J Neurosci 24:1–6
Liu L, Chen L, Liedtke W, Simon S (2007) Changes in osmolality sensitize the response to capsaicin in trigeminal sensory neurons. J Neurophysiol 97:2001–2015
Liu B, Yao J, Wang Y, Li H, Qin F (2009) Proton inhibition of unitary currents of vanilloid receptors. J Gen Physiol 134:243–258
Luebbert M, Radtke D, Wodarski R, Damann N, Hatt H, Wetzel CH (2010) Direct activation of transient receptor potential V1 by nickel ions. Pflugers Arch 459:737–750
Lukacs V, Thyagarajan B, Varnai P, Balla A, Balla T, Rohacs T (2007) Dual regulation of TRPV1 by phosphoinositides. J Neurosci 27:7070–7080
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 35:471–478
Matsumoto K, Hosoya T, Tashima K, Namiki T, Murayama T, Horie S (2011) Distribution of transient receptor potential vanilloid 1 channel-expressing nerve fibers in mouse rectal and colonic enteric nervous system: relationship to peptidergic and nitrergic neurons. Neuroscience 172:518–534
Matta JA, Ahern GP (2007) Voltage is a partial activator of thermo-sensitive TRP channels. J Physiol
Matta JA, Miyares RL, Ahern GP (2007) TRPV1 is a novel target for omega-3 polyunsaturated fatty acids. J Physiol 578:397–411
Mccleverty C, Koesema E, Patapoutian A, Lesley S, Kreusch A (2006) Crystal structure of the human TRPV2 channel ankyrin repeat domain. Protein Sci 2201–2206
Mederos y Schnitzler M, Storch U, Gudermann T (2011) AT1 receptors as mechanosensors. Curr Opin Pharmacol 11:112–116
Minke B (1977) Drosophila mutant with a transducer defect. Biophys Struct Mech 3:59–64
Miranda A, Nordstrom E, Mannem A, Smith C, Banerjee B, Sengupta JN (2007) The role of transient receptor potential vanilloid 1 in mechanical and chemical visceral hyperalgesia following experimental colitis. Neuroscience
Mochizuki T, Sokabe T, Araki I, Fujishita K, Shibasaki K, Uchida K, Naruse K, Koizumi S, Takeda M, Tominaga M (2009) The TRPV4 cation channel mediates stretch-evoked Ca2+ influx and ATP release in primary urothelial cell cultures. J Biol Chem 284:21257–21264
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 278:50080–50090
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 280:13424–13432
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 105:7451–7455
Montell C (2011) The history of TRP channels, a commentary and reflection. Pflugers Arch 461:499–506
Montell C, Rubin GM (1989) Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron 2:1313–1323
Moriyama T, Iida T, Kobayashi K, Higashi T, Fukuoka T, Tsumura H, Leon C, Suzuki N, Inoue K, Gachet C, Noguchi K, Tominaga M (2003) Possible involvement of P2Y2 metabotropic receptors in ATP-induced transient receptor potential vanilloid receptor 1-mediated thermal hypersensitivity. J Neurosci 23:6058–6062
Morenilla-Palao C, Planells-Cases R, García-Sanz N, Ferrer-Montiel A (2004) Regulated exocytosis contributes to protein kinase C potentiation of vanilloid receptor activity. J Biol Chem 279:25665–25672
Moriyama T, Higashi T, Togashi K, Iida T, Segi E, Sugimoto Y, Tominaga T, Narumiya S, Tominaga M (2005) Sensitization of TRPV1 by EP1 and IP reveals peripheral nociceptive mechanism of prostaglandins. Mol Pain 1:3
Movahed P, Jonsson BA, Birnir B, Wingstrand JA, Jorgensen TD, Ermund A, Sterner O, Zygmunt PM, Hogestatt ED (2005) Endogenous unsaturated C18 N-acylethanolamines are vanilloid receptor (TRPV1) agonists. J Biol Chem 280:38496–38504
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 58:362–373
Nieto-Posadas A, Picazo-Juárez G, Llorente I, Jara-Oseguera A, Morales-Lázaro S, Escalante-Alcalde D, Islas LD, Rosenbaum T (2011) Lysophosphatidic acid directly activates TRPV1 through a C-terminal binding site. Nat Chem Biol 8: 78–85
Nilius B, Talavera K, Owsianik G, Prenen J, Droogmans G, Voets T (2005) Gating of TRP channels: a voltage connection? J Physiol 567:35–44.
Nishihara E, Hiyama T Y, Noda M (2011) Osmosensitivity of transient receptor potential vanilloid 1 is synergistically enhanced by distinct activating stimuli such as temperature and protons. PLoS One 6:e22246
Novakova-Tousova K, Vyklicky L, Susankova K, Benedikt J, Samad A, Teisinger J, Vlachova V (2007) Functional changes in the vanilloid receptor subtype 1 channel during and after acute desensitization. J Neurosci 149:144–154
Numazaki M, Tominaga T, Toyooka H, Tominaga M (2002) Direct phosphorylation of capsaicin receptor VR1 by protein kinase Cepsilon and identification of two target serine residues. J Biol Chem 277:13375–13378
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 100:8002–8006
Obreja O, Rathee PK, Lips KS, Distler C, Kress M (2002) IL-1 beta potentiates heat-activated currents in rat sensory neurons: involvement of IL-1RI, tyrosine kinase, and protein kinase C. Faseb J 16:1497–1503
Ohta T, Ikemi Y, Murakami M, Imagawa T, Otsuguro K, Ito S (2006) Potentiation of transient receptor potential V1 functions by the activation of metabotropic 5-HT receptors in rat primary sensory neurons. J Physiol 576:809–822
Ohta T, Imagawa T, Ito S (2008) Novel gating and sensitizing mechanism of capsaicin receptor (TRPV1): tonic inhibitory regulation of extracellular sodium through the external protonation sites on TRPV1. J Biol Chem 283:9377–9387
Olah Z, Karai L, Iadarola MJ (2002) Protein kinase C(alpha) is required for vanilloid receptor 1 activation. Evidence for multiple signaling pathways. J Biol Chem 277:35752–35759
Oliet SH, Bourque CW (1992) Properties of supraoptic magnocellular neurones isolated from the adult rat. J Physiol 455:291–306
Oliet SH, Bourque CW (1993) Mechanosensitive channels transduce osmosensitivity in supraoptic neurons. Nature 364:341–343
Oseguera AJ, Islas LD, Garcia-Villegas R, Rosenbaum T (2007) On the mechanism of TBA block of the TRPV1 channel. Biophys J 92:3901–3914
Pan HL, Zhang YQ, Zhao ZQ (2010) Involvement of lysophosphatidic acid in bone cancer pain by potentiation of TRPV1 via PKCepsilon pathway in dorsal root ganglion neurons. Mol Pain 6:85
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 103:11393–11398
Patwardhan AM, Scotland PE, Akopian AN, Hargreaves KM (2009) Activation of TRPV1 in the spinal cord by oxidized linoleic acid metabolites contributes to inflammatory hyperalgesia. Proc Natl Acad Sci USA 106:18820–18824
Patwardhan AM, Akopian AN, Ruparel NB, Diogenes A, Weintraub ST, Uhlson C, Murphy RC, Hargreaves KM (2011) Heat generates oxidized linoleic acid metabolites that activate TRPV1 and produce pain in rodents. J Clin Invest 120:1617–1626
Petersen M, LaMotte RH (1993) Effect of protons on the inward current evoked by capsaicin in isolated dorsal root ganglion cells. Pain 54:37–42
Petrosino S, Iuvone T, Di Marzo V (2010) N-palmitoyl-ethanolamine: Biochemistry and new therapeutic opportunities. Biochimie 92:724–727
Picazo-Juarez G, Romero-Suarez S, Nieto-Posadas A, Llorente I, Jara-Oseguera A, Briggs M, McIntosh TJ, Simon SA, Ladron-de-Guevara E, Islas LD, Rosenbaum T (2011) Identification of a binding motif in the S5 helix that confers cholesterol sensitivity to the TRPV1 ion channel. J Biol Chem 286:24966–24976
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
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 432:549–556
Premkumar LS, Ahern GP (2000) Induction of vanilloid receptor channel activity by protein kinase C. Nature 408:985–990
Premkumar LS, Agarwal S, Steffen D (2002) Single-channel properties of native and cloned rat vanilloid receptors. J Physiol 545:107–117
Premkumar LS, Qi ZH, Van Buren J, Raisinghani M (2004) Enhancement of potency and efficacy of NADA by PKC-mediated phosphorylation of vanilloid receptor. J Neurophysiol 91:1442–1449
Prescott ED, Julius D (2003) A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity. Science 300:1284–1288
Puntambekar P, Van Buren J, Raisinghani M, Premkumar LS, Ramkumar V (2004) Direct interaction of adenosine with the TRPV1 channel protein. J Neurosci 24:3663–3671
Rathee P, Distler C, Obreja O, Neuhuber W, Wang G, Wang S, Nau C, Kress M (2002) PKA/AKAP/VR-1 module: A common link of Gs-mediated signaling to thermal hyperalgesia. J Neurosci 22:4740–4745
Ravnefjord A, Brusberg M, Kang D, Bauer U, Larsson H, Lindstrom E, Martinez V (2009) Involvement of the transient receptor potential vanilloid 1 (TRPV1) in the development of acute visceral hyperalgesia during colorectal distension in rats. Eur J Pharmacol 611:85–91
Ristoiu V, Shibasaki K, Uchida K, Zhou Y, Ton BH, Flonta ML, Tominaga M (2011) Hypoxia-induced sensitization of transient receptor potential vanilloid 1 involves activation of hypoxia-inducible factor-1 alpha and PKC. Pain 152:936–945
Robinson DR, McNaughton PA, Evans ML, Hicks GA (2004) Characterization of the primary spinal afferent innervation of the mouse colon using retrograde labelling. Neurogastroenterol Motil 16:113–124
Rodriguez BM, Sigg D, Bezanilla F (1998) Voltage gating of Shaker K+channels. The effect of temperature on ionic and gating currents. J Gen Physiol 112:223–242
Rodriguez de Fonseca F, Navarro M, Gomez R, Escuredo L, Nava F, Fu J, Murillo-Rodriguez E, Giuffrida A, LoVerme J, Gaetani S, Kathuria S, Gall C, Piomelli D (2001) An anorexic lipid mediator regulated by feeding. Nature 414:209–212
Rong W, Hillsley K, Davis JB, Hicks G, Winchester WJ, Grundy D (2004) Jejunal afferent nerve sensitivity in wild-type and TRPV1 knockout mice. J Physiol 560:867–881
Rosenbaum T, Gordon-Shaag A, Munari M, Gordon S E (2004) Ca2+/calmodulin modulates TRPV1 activation by capsaicin. J Gen Physiol 123:53–62
Ross RA, Gibson TM, Brockie HC, Leslie M, Pashmi G, Craib SJ, Di Marzo V, Pertwee RG (2001) Structure-activity relationship for the endogenous cannabinoid, anandamide, and certain of its analogues at vanilloid receptors in transfected cells and vas deferens. Br J Pharmacol 132:631–640
Ryu S, Liu B, Qin F (2003) Low pH potentiates both capsaicin binding and channel gating of VR1 receptors. J Gen Physiol 122:45–61
Ryu S, Liu B, Yao J, Fu Q, Qin F (2007) Uncoupling proton activation of vanilloid receptor TRPV1. J Neurosci 27:12797–12807
Salazar H, Jara-Oseguera A, Hernandez-Garcia E, Llorente I, Arias O, II, Soriano-Garcia M, Islas LD, Rosenbaum T (2009) Structural determinants of gating in the TRPV1 channel. Nat Struct Mol Biol 16:704–710
Salazar H, Llorente I, Jara-Oseguera A, Garcia-Villegas R, Munari M, Gordon SE, Islas LD, Rosenbaum T (2008) A single N-terminal cysteine in TRPV1 determines activation by pungent compounds from onion and garlic. Nat Neurosci 11:255–261
Samuelsson B (1983) Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation. Science 220:568–575
Samways DS, Egan TM (2011) Calcium-dependent decrease in the single-channel conductance of TRPV1. Pflugers Arch 62:681–691
Samways DS, Khakh BS, Egan TM (2008) Tunable calcium current through TRPV1 receptor channels. J Biol Chem 283:31274–31278
Sawynok J, Liu XJ (2003) Adenosine in the spinal cord and periphery: release and regulation of pain. Prog Neurobiol 69:313–340
Scotland RS, Chauhan S, Davis C, De Felipe C, Hunt S, Kabir J, Kotsonis P, Oh U, Ahluwalia A (2004) Vanilloid receptor TRPV1, sensory C-fibers, and vascular autoregulation: a novel mechanism involved in myogenic constriction. Circ Res 95:1027–1034
Sculptoreanu A, Kullmann FA, Artim DE, Bazley FA, Schopfer F, Woodcock S, Freeman BA, de Groat WC (2010) Nitro-oleic acid inhibits firing and activates TRPV1- and TRPA1-mediated inward currents in dorsal root ganglion neurons from adult male rats. J Pharmacol Exp Ther 333:883–895
Schnizler K, Shutov LP, Van Kanegan MJ, Merrill MA, Nichols B, McKnight GS, Strack S, Hell JW, Usachev YM (2008) Protein kinase A anchoring via AKAP150 is essential for TRPV1 modulation by forskolin and prostaglandin E2 in mouse sensory neurons. J Neurosci 28:4904–4917
Schoppa NE, McCormack K, Tanouye MA, Sigworth FJ (1992) The size of gating charge in wild-type and mutant Shaker potassium channels. Science 255:1712–1715
Sharif Naeini R, Witty MF, Seguela P, Bourque CW (2006) An N-terminal variant of Trpv1 channel is required for osmosensory transduction. Nat Neurosci 9:93–98
Sharif-Naeini R, Ciura S, Bourque CW (2008) TRPV1 gene required for thermosensory transduction and anticipatory secretion from vasopressin neurons during hyperthermia. Neuron 58:179–185
Shim WS, Tak MH, Lee MH, Kim M, Kim M, Koo JY, Lee CH, Kim M, Oh U (2007) TRPV1 mediates histamine-induced itching via the activation of phospholipase A2 and 12-lipoxygenase. J Neurosci 27:2331–2337
Shin J, Cho H, Hwang SW, Jung J, Shin CY, Lee SY, Kim SH, Lee MG, Choi YH, Kim J, Haber NA, Reichling DB, Khasar S, Levine JD, Oh U (2002) Bradykinin-12-lipoxygenase-VR1 signaling pathway for inflammatory hyperalgesia. Proc Natl Acad Sci USA 99:10150–10155
Smart D, Gunthorpe MJ, Jerman JC, Nasir S, Gray J, Muir AI, Chambers JK, Randall AD, Davis JB (2000) The endogenous lipid anandamide is a full agonist at the human vanilloid receptor (hVR1). Br J Pharmacol 129:227–230
Smart D, Jonsson KO, Vandevoorde S, Lambert DM, Fowler CJ (2002) ‘Entourage’ effects of N-acyl ethanolamines at human vanilloid receptors. Comparison of effects upon anandamide-induced vanilloid receptor activation and upon anandamide metabolism. Br J Pharmacol 136:452–458
Spencer NJ, Kerrin A, Singer CA, Hennig GW, Gerthoffer WT, McDonnell O (2008) Identification of capsaicin-sensitive rectal mechanoreceptors activated by rectal distension in mice. Neuroscience 153:518–534
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 128:509–522
Sugiuar T, Bielefeldt K, Gebhart GF (2004) TRPV1 function in mouse colon sensory neurons is enhanced by metabotropic 5-hydroxytryptamine receptor activation. J Neurosci 24:9521–9530
Sun H, Li DP, Chen SR, Hittelman WN, Pan HL (2009) Sensing of blood pressure increase by transient receptor potential vanilloid 1 receptors on baroreceptors. J Pharmacol Exp Ther 331:851–859
Susankova K, Tousova K, Vyklicky L, Teisinger J, Vlachova V (2006) Reducing and oxidizing agents sensitize heat-activated vanilloid receptor (TRPV1) current. Mol Pharmacol 70:383–394
Susankova K, Ettrich R, Vyklicky L, Teisinger J, Vlachova V (2007) Contribution of the putative inner-pore region to the gating of the transient receptor potential vanilloid subtype 1 channel (TRPV1). J Neurosci 27:7578–7585
Sutton KG, Garrett EM, Rutter AR, Bonnert TP, Jarolimek W, Seabrook GR (2005) Functional characterisation of the S512Y mutant vanilloid human TRPV1 receptor. Br J Pharmacol 146:702–711
Szallasi A, Blumberg PM (1989) Resiniferatoxin, a phorbol-related diterpene, acts as an ultrapotent analog of capsaicin, the irritant constituent in red pepper. Neuroscience 30:515–520
Szallasi A, Blumberg PM (1991) Characterization of vanilloid receptors in the dorsal horn of pig spinal cord. Brain Res 547:335–338
Szallasi A, Blumberg PM (1993) [3H]resiniferatoxin binding by the vanilloid receptor: species-related differences, effects of temperature and sulfhydryl reagents. Naunyn Schmiedebergs Arch Pharmacol 347:84–91
Szallasi A, Blumberg PM (1999) Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev 51:159–212
Szallasi A, Conte B, Goso C, Blumberg PM, Manzini S (1993a) Characterization of a peripheral vanilloid (capsaicin) receptor in the urinary bladder of the rat. Life Sci 52:PL221–226
Szallasi A, Lewin NA, Blumberg PM (1993b) Vanilloid (capsaicin) receptor in the rat: positive cooperativity of resiniferatoxin binding and its modulation by reduction and oxidation. J Pharmacol Exp Ther 266:678–683
Szoke E, Borzsei R, Toth DM, Lengl O, Helyes Z, Sandor Z, Szolcsanyi J (2011) Effect of lipid raft disruption on TRPV1 receptor activation of trigeminal sensory neurons and transfected cell line. Eur J Pharmacol 628:67–74
Tan LL, Bornstein JC, Anderson CR (2008) Distinct chemical classes of medium-sized transient receptor potential channel vanilloid 1-immunoreactive dorsal root ganglion neurons innervate the adult mouse jejunum and colon. Neuroscience 156:334–343
Taylor AC, McCarthy JJ, Stocker SD (2008) Mice lacking the transient receptor vanilloid potential 1 channel display normal thirst responses and central Fos activation to hypernatremia. Am J Physiol Regul Integr Comp Physiol 294:R1285–1293
Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D (1998) The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21:531–543
Tominaga M, Wada M, Masu M (2001) Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia. Proc Natl Acad Sci USA 98:6951–6956
Tousova K, Vyklicky L, Susankova K, Benedikt J, Vlachova V (2005) Gadolinium activates and sensitizes the vanilloid receptor TRPV1 through the external protonation sites. Mol Cell Neurosci 30:207–217
Ufret-Vincenty CA, Klein RM, Hua L, Angueyra J, Gordon SE (2011) Localization of the PIP2 sensor of TRPV1 ion channels. J Biol Chem 286:9688–9698
Valdes AM, De Wilde G, Doherty SA, Lories RJ, Vaughn FL, Laslett LL, Maciewicz RA, Soni A, Hart DJ, Zhang W, Muir KR, Dennison EM, Wheeler M, Leaverton P, Cooper C, Spector TD, Cicuttini FM, Chapman V, Jones G, Arden NK, Doherty M (2011) The Ile585Val TRPV1 variant is involved in risk of painful knee osteoarthritis. Ann Rheum Dis 70:1556–1561
Valente P, García-Sanz N, Gomis A, Fernandez-Carvajal A, Fernandez-Ballester G, Viana F, Belmonte C, Ferrer-Montiel A (2008) Identification of molecular determinants of channel gating in the transient receptor potential box of vanilloid receptor I. Faseb J 22:3298–3309
Valente P, Fernandez-Carvajal A, Camprubi-Robles M, Gomis A, Quirce S, Viana F, Fernandez-Ballester G, Gonzalez-Ros JM, Belmonte C, Planells-Cases R, Ferrer-Montiel A (2011) Membrane-tethered peptides patterned after the TRP domain (TRPducins) selectively inhibit TRPV1 channel activity. Faseb J 25:1628–1640
Van Buren JJ, Bhat S, Rotello R, Pauza ME, Premkumar LS (2005) Sensitization and translocation of TRPV1 by insulin and IGF-I. Mol Pain 1:17
Vay L, Gu C, McNaughton PA (2011) The thermo-TRP ion channel family: properties and therapeutic implications. Br J Pharmacol
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 534:813–825
Venkatachalam K, Montell C (2007) TRP channels. Annu Rev Biochem 76:387–417
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 23:1340–1350
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 430:748–754
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 3:174–182
Vyklicky L, Lyfenko A, Susankova K, Teisinger J, Vlachova V (2002) Reducing agent dithiothreitol facilitates activity of the capsaicin receptor VR-1. Neuroscience 111:435–441
Walpole CS, Wrigglesworth R, Bevan S, Campbell EA, Dray A, James IF, Masdin K J, Perkins MN, Winter J (1993) Analogues of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 3. The hydrophobic side-chain “C-region”. J Med Chem 36:2381–2389
Wang Y, Kedei N, Wang M, Wang QJ, Huppler AR, Toth A, Tran R, Blumberg PM (2004) Interaction between protein kinase Cmu and the vanilloid receptor type 1. J Biol Chem 279:53674–53682
Wang X, Miyares RL, Ahern GP (2005) Oleoylethanolamide excites vagal sensory neurones, induces visceral pain and reduces short-term food intake in mice via capsaicin receptor TRPV1. J Physiol 564:541–547
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 285:11547–11556
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 97:13889–13894
Woo D, Jung S, Zhu M, Park C, Kim Y, Oh S, Lee C (2008) Direct activation of transient receptor potential vanilloid 1(TRPV1) by diacylglycerol (DAG). Mol Pain. 1:4:42
Xu X, Gordon E, Lin Z, Lozinskaya I M, Chen Y, Thorneloe K S (2009) Functional TRPV4 channels and an absence of capsaicin-evoked currents in freshly-isolated, guinea-pig urothelial cells. Channels (Austin) 3:156–160
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 57:277–287
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
Yao J, Qin F (2009) Interaction with phosphoinositides confers adaptation onto the TRPV1 pain receptor. PLoS Biol 7:e46
Yao J, Liu B, Qin F (2009) Rapid temperature jump by infrared diode laser irradiation for patch-clamp studies. Biophys J 96:3611–3619
Yao J, Liu B, Qin F (2010a) Kinetic and energetic analysis of thermally activated TRPV1 channels. Biophys J 99:1743–1753
Yao J, Liu B, Qin F (2010b) Pore turret of thermal TRP channels is not essential for temperature sensing. Proc Natl Acad Sci USA 107:E125; author reply E126–127
Yao J, Liu B, Qin F (2011) Modular thermal sensors in temperature-gated transient receptor potential (TRP) channels. Proc Natl Acad Sci USA 108:11109–11114
Yokoyama T, Saito T, Ohbuchi T, Hashimoto H, Suzuki H, Otsubo H, Fujihara H, Nagatomo T, Ueta Y (2010) TRPV1 gene deficiency attenuates miniature EPSC potentiation induced by mannitol and angiotensin II in supraoptic magnocellular neurons. J Neurosci 30:876–884
Yu W, Hill WG, Apodaca G, Zeidel ML (2011) Expression and distribution of transient receptor potential (TRP) channels in bladder epithelium. Am J Physiol Renal Physiol 300:F49–59
Zhang Z, Bourque CW (2008) Amplification of transducer gain by angiotensin II-mediated enhancement of cortical actin density in osmosensory neurons. J Neurosci 28:9536–9544
Zhang N, Inan S, Cowan A, Sun R, Wang JM, Rogers TJ, Caterina M, Oppenheim J J (2005a) A proinflammatory chemokine, CCL3, sensitizes the heat- and capsaicin-gated ion channel TRPV1. Proc Natl Acad Sci USA 102:4536–4541
Zhang X, Huang J, McNaughton PA (2005b) NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. Embo J 24:4211–4223
Zhang H, Cang CL, Kawasaki Y, Liang LL, Zhang YQ, Ji RR, Zhao ZQ (2007a) Neurokinin-1 receptor enhances TRPV1 activity in primary sensory neurons via PKCepsilon: a novel pathway for heat hyperalgesia. J Neurosci 27:12067–12077
Zhang Z, Kindrat AN, Sharif-Naeini R, Bourque CW (2007b) Actin filaments mediate mechanical gating during osmosensory transduction in rat supraoptic nucleus neurons. J Neurosci 27:4008–4013
Zhang X, Li L, McNaughton PA (2008) Proinflammatory mediators modulate the heat-activated ion channel TRPV1 via the scaffolding protein AKAP79/150. Neuron 59:450–461
Zhang F, Liu S, Yang F, Zheng J, Wang K (2011a) Identification of a tetrameric assembly domain in the C terminus of heat-activated TRPV1 channels. J Biol Chem 286:15308–15316
Zhang X, Daugherty SL, de Groat WC (2011b) 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:R644–654
Zhuang ZY, Xu H, Clapham D E, Ji RR (2004) Phosphatidylinositol 3-kinase activates ERK in primary sensory neurons and mediates inflammatory heat hyperalgesia through TRPV1 sensitization. J Neurosci 24:8300–8309
Zygmunt PM, Petersson J, Andersson DA, Chuang H, Sorgard M, Di Marzo V, Julius D, Hogestatt ED (1999) Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400:452–457
Acknowledgements
This work was supported by grants from PAPIIT IN204111, CONACyT CB-129474 and a Grant from Fundación Miguel Alemán to T.R.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Rosenbaum, T., Jara-Oseguera, A. (2012). TRPV1 in Cell Signaling: Molecular Mechanisms of Function and Modulation. In: Kamkin, A., Lozinsky, I. (eds) Mechanically Gated Channels and their Regulation. Mechanosensitivity in Cells and Tissues, vol 6. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5073-9_3
Download citation
DOI: https://doi.org/10.1007/978-94-007-5073-9_3
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-5072-2
Online ISBN: 978-94-007-5073-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)