Structure and function of TRPV1

Capsaicin, the main ingredient in hot chili peppers, elicits a sensation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system. The capsaicin receptor, transient receptor potential vanilloid 1 (TRPV1), is predicted to have six transmembrane (TM) domains and a short, pore-forming hydrophobic stretch between the fifth and sixth TM domains, and is activated not only by capsaicin but also by heat (>43°C), acid and various lipids. Within the TPRV1 protein, many regions and amino acids involved in specific functions (multimerization, capsaicin action, proton action, heat activation, desensitization, permeability, phosphorylation and modulation by lipids) have been identified since the cloning in 1997. Given the fact that TRPV1 is a key molecule in peripheral nociception, these regions and amino acids could prove useful for the development of novel anti-nociceptive or anti-inflammatory agents.

[1]  R. Huganir,et al.  Calmodulin Mediates Calcium-Dependent Inactivation of N-Methyl-D-Aspartate Receptors , 1998, Neuron.

[2]  L. Premkumar,et al.  Single‐channel properties of native and cloned rat vanilloid receptors , 2002, The Journal of physiology.

[3]  J. Tate,et al.  Potassium channels: structures, models, simulations. , 2002, Biochimica et biophysica acta.

[4]  S. Simon,et al.  The activation mechanism of rat vanilloid receptor 1 by capsaicin involves the pore domain and differs from the activation by either acid or heat. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[5]  M. Tominaga,et al.  Activation of protein kinase C reverses capsaicin-induced calcium-dependent desensitization of TRPV1 ion channels. , 2004, Cell calcium.

[6]  Yi Dai,et al.  Proteinase-Activated Receptor 2-Mediated Potentiation of Transient Receptor Potential Vanilloid Subfamily 1 Activity Reveals a Mechanism for Proteinase-Induced Inflammatory Pain , 2004, The Journal of Neuroscience.

[7]  R. Prinjha,et al.  Voltage‐ and time‐dependent properties of the recombinant rat vanilloid receptor (rVR1) , 2000, The Journal of physiology.

[8]  L. Vyklický,et al.  Reducing agent dithiothreitol facilitates activity of the capsaicin receptor VR-1 , 2002, Neuroscience.

[9]  T. Fukuoka,et al.  Possible Involvement of P2Y2 Metabotropic Receptors in ATP-Induced Transient Receptor Potential Vanilloid Receptor 1-Mediated Thermal Hypersensitivity , 2003, The Journal of Neuroscience.

[10]  M. Tominaga,et al.  Thermosensation and pain. , 2004, Journal of neurobiology.

[11]  D. J. Brasier,et al.  cAMP-Dependent Protein Kinase Regulates Desensitization of the Capsaicin Receptor (VR1) by Direct Phosphorylation , 2002, Neuron.

[12]  Yun Wang,et al.  Interaction between protein kinase Cmu and the vanilloid receptor type 1. , 2004, The Journal of biological chemistry.

[13]  S. Hwang,et al.  Capsaicin Binds to the Intracellular Domain of the Capsaicin-Activated Ion Channel , 1999, The Journal of Neuroscience.

[14]  D. Julius,et al.  Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide , 1999, Nature.

[15]  David Julius,et al.  Molecular Basis for Species-Specific Sensitivity to “Hot” Chili Peppers , 2002, Cell.

[16]  L. Dekker,et al.  Specific Involvement of PKC-ε in Sensitization of the Neuronal Response to Painful Heat , 1999, Neuron.

[17]  A. Basbaum,et al.  Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition , 2001, Nature.

[18]  M. Tominaga,et al.  Direct Phosphorylation of Capsaicin Receptor VR1 by Protein Kinase Cε and Identification of Two Target Serine Residues* , 2002, The Journal of Biological Chemistry.

[19]  D. McKemy,et al.  Lessons from peppers and peppermint: the molecular logic of thermosensation , 2003, Current Opinion in Neurobiology.

[20]  Attila Toth,et al.  Molecular Determinants of Vanilloid Sensitivity in TRPV1* , 2004, Journal of Biological Chemistry.

[21]  C. Harteneck.  Proteins modulating TRP channel function. , 2003, Cell calcium.

[22]  D. Julius,et al.  Acid potentiation of the capsaicin receptor determined by a key extracellular site. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Pierangelo Geppetti,et al.  An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[24]  M. Raisinghani,et al.  Enhancement of potency and efficacy of NADA by PKC-mediated phosphorylation of vanilloid receptor. , 2004, Journal of neurophysiology.

[25]  S. Simon,et al.  Capsaicin-induced currents with distinct desensitization and Ca2+ dependence in rat trigeminal ganglion cells. , 1996, Journal of neurophysiology.

[26]  M. Kress,et al.  PKA/AKAP/VR-1 Module: A Common Link of Gs-Mediated Signaling to Thermal Hyperalgesia , 2002, The Journal of Neuroscience.

[27]  P. Pasricha,et al.  Modulation of TRPV1 by nonreceptor tyrosine kinase, c-Src kinase. , 2004, American journal of physiology. Cell physiology.

[28]  U. Kaupp,et al.  Cyclic nucleotide-gated ion channels. , 2002, Physiological reviews.

[29]  Craig Montell,et al.  The TRP Superfamily of Cation Channels , 2005, Science's STKE.

[30]  D. Mohapatra,et al.  Desensitization of Capsaicin-activated Currents in the Vanilloid Receptor TRPV1 Is Decreased by the Cyclic AMP-dependent Protein Kinase Pathway* , 2003, Journal of Biological Chemistry.

[31]  P. Blumberg,et al.  Vanilloid (Capsaicin) receptors and mechanisms. , 1999, Pharmacological reviews.

[32]  J. Levine,et al.  A Novel Nociceptor Signaling Pathway Revealed in Protein Kinase C ε Mutant Mice , 1999, Neuron.

[33]  S. Simon,et al.  Capsaicin activated currents in rat dorsal root ganglion cells , 1996, Pain.

[34]  K. Deisseroth,et al.  Calmodulin supports both inactivation and facilitation of L-type calcium channels , 1999, Nature.

[35]  G. Rubin,et al.  Molecular characterization of the drosophila trp locus: A putative integral membrane protein required for phototransduction , 1989, Neuron.

[36]  S. Smerdon,et al.  The ankyrin repeat: a diversity of interactions on a common structural framework. , 1999, Trends in biochemical sciences.

[37]  D. J. Brasier,et al.  Protein kinase C phosphorylation sensitizes but does not activate the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1) , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[38]  J. Adelman,et al.  Erratum: Calmodulin is the Ca2+ sensor for Ca2+-dependent inactivation of L-type calcium channels (Neuron (March 1999)) , 1999 .

[39]  S. Hwang,et al.  Phosphorylation of Vanilloid Receptor 1 by Ca2+/Calmodulin-dependent Kinase II Regulates Its Vanilloid Binding* , 2004, Journal of Biological Chemistry.

[40]  M. Tominaga,et al.  Bradykinin lowers the threshold temperature for heat activation of vanilloid receptor 1. , 2002, Journal of neurophysiology.

[41]  Sunghoon Kim,et al.  Agonist Recognition Sites in the Cytosolic Tails of Vanilloid Receptor 1* , 2002, The Journal of Biological Chemistry.

[42]  David E. Clapham,et al.  TRP channels as cellular sensors , 2003, Nature.

[43]  A. Basbaum,et al.  The Cloned Capsaicin Receptor Integrates Multiple Pain-Producing Stimuli , 1998, Neuron.

[44]  Peter M. Blumberg,et al.  Analysis of the Native Quaternary Structure of Vanilloid Receptor 1* 210 , 2001, The Journal of Biological Chemistry.

[45]  T. Baumann,et al.  Extracellular Protons Both Increase the Activity and Reduce the Conductance of Capsaicin- Gated Channels , 2000, The Journal of Neuroscience.

[46]  G. Ahern.  Activation of TRPV1 by the Satiety Factor Oleoylethanolamide* , 2003, Journal of Biological Chemistry.

[47]  A. Gordon-Shaag,et al.  Ca2+/Calmodulin Modulates TRPV1 Activation by Capsaicin , 2004, The Journal of general physiology.

[48]  L. Premkumar,et al.  Induction of vanilloid receptor channel activity by protein kinase C , 2000, Nature.

[49]  C. Zuker,et al.  Calmodulin Regulation of Drosophila Light-Activated Channels and Receptor Function Mediates Termination of the Light Response In Vivo , 1997, Cell.

[50]  Bernd Nilius,et al.  The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels , 2004, Nature.

[51]  Richard E Middleton,et al.  Resiniferatoxin binds to the capsaicin receptor (TRPV1) near the extracellular side of the S4 transmembrane domain. , 2004, Biochemistry.

[52]  S. Bevan,et al.  A study of the voltage dependence of capsaicin‐activated membrane currents in rat sensory neurones before and after acute desensitization , 1999, The Journal of physiology.

[53]  D. Julius,et al.  The vanilloid receptor: a molecular gateway to the pain pathway. , 2001, Annual review of neuroscience.

[54]  P. Anand,et al.  TRPV3 is a temperature-sensitive vanilloid receptor-like protein , 2002, Nature.

[55]  M. Tominaga,et al.  Structural determinant of TRPV1 desensitization interacts with calmodulin , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[56]  C. Maggi,et al.  Capsaicin and primary afferent neurons: from basic science to human therapy? , 1991, Journal of the autonomic nervous system.

[57]  A. Patapoutian,et al.  ThermoTRP channels and beyond: mechanisms of temperature sensation , 2003, Nature Reviews Neuroscience.

[58]  V. Ramkumar,et al.  Direct Interaction of Adenosine with the TRPV1 Channel Protein , 2004, The Journal of Neuroscience.

[59]  A. Ferrer-Montiel,et al.  Identification of an Aspartic Residue in the P-loop of the Vanilloid Receptor That Modulates Pore Properties* , 2000, The Journal of Biological Chemistry.

[60]  R. Gereau,et al.  Prostaglandin and Protein Kinase A-Dependent Modulation of Vanilloid Receptor Function by Metabotropic Glutamate Receptor 5: Potential Mechanism for Thermal Hyperalgesia , 2002, The Journal of Neuroscience.

[61]  S. Siegelbaum,et al.  Hyperpolarization-activated cation currents: from molecules to physiological function. , 2003, Annual review of physiology.

[62]  D. Julius,et al.  The capsaicin receptor: a heat-activated ion channel in the pain pathway , 1997, Nature.

[63]  M. Tominaga,et al.  Sensitization of TRPV1 by EP1 and IP reveals peripheral nociceptive mechanism of prostaglandins , 2005, Molecular pain.

[64]  M. Masu,et al.  Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[65]  D. Hilgemann,et al.  Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gβγ , 1998, Nature.

[66]  R. Huganir,et al.  Inactivation of NMDA Receptors by Direct Interaction of Calmodulin with the NR1 Subunit , 1996, Cell.

[67]  G S Oxford,et al.  The Role of Calcium in the Desensitization of Capsaicin Responses in Rat Dorsal Root Ganglion Neurons , 1997, The Journal of Neuroscience.

[68]  C. Montell,et al.  Requirement for the PDZ Domain Protein, INAD, for Localization of the TRP Store-Operated Channel to a Signaling Complex , 1997, Neuron.

[69]  M. Iadarola,et al.  Protein Kinase Cα Is Required for Vanilloid Receptor 1 Activation , 2002, The Journal of Biological Chemistry.

[70]  D. Mohapatra,et al.  A tyrosine residue in TM6 of the Vanilloid Receptor TRPV1 involved in desensitization and calcium permeability of capsaicin-activated currents , 2003, Molecular and Cellular Neuroscience.

[71]  D. Clapham,et al.  The TRPM7 channel is inactivated by PIP2 hydrolysis , 2002, Nature Cell Biology.

[72]  R. Molday.  Calmodulin regulation of cyclic-nucleotide-gated channels , 1996, Current Opinion in Neurobiology.

[73]  L. Vyklický,et al.  Functional Role of C-Terminal Cytoplasmic Tail of Rat Vanilloid Receptor 1 , 2003, The Journal of Neuroscience.

[74]  T. Bisogno,et al.  The vanilloid receptor (VR1)‐mediated effects of anandamide are potently enhanced by the cAMP‐dependent protein kinase , 2001, Journal of neurochemistry.

[75]  A. Gordon-Shaag,et al.  Ca 2 / Calmodulin Modulates TRPV 1 Activation by Capsaicin , 2003 .

[76]  Peter McIntyre,et al.  Identification of Species-specific Determinants of the Action of the Antagonist Capsazepine and the Agonist PPAHV on TRPV1* , 2004, Journal of Biological Chemistry.

[77]  Hong Wang,et al.  Functional Analysis of Capsaicin Receptor (Vanilloid Receptor Subtype 1) Multimerization and Agonist Responsiveness Using a Dominant Negative Mutation , 2001, The Journal of Neuroscience.

[78]  S. Bevan,et al.  Inhibition of calcineurin inhibits the desensitization of capsaicin-evoked currents in cultured dorsal root ganglion neurones from adult rats , 2006, Pflügers Archiv.

[79]  D. T. Yue,et al.  Calmodulin Is the Ca2+ Sensor for Ca2+-Dependent Inactivation of L-Type Calcium Channels , 1999, Neuron.

[80]  G. Schultz,et al.  TRPV1 Acts as Proton Channel to Induce Acidification in Nociceptive Neurons* , 2004, Journal of Biological Chemistry.

[81]  D. Julius,et al.  The Super-Cooling Agent Icilin Reveals a Mechanism of Coincidence Detection by a Temperature-Sensitive TRP Channel , 2004, Neuron.

[82]  S. Hwang,et al.  Direct activation of capsaicin receptors by products of lipoxygenases: endogenous capsaicin-like substances. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[83]  D. Julius,et al.  A Modular PIP2 Binding Site as a Determinant of Capsaicin Receptor Sensitivity , 2003, Science.