Skip to main content
SpringerLink
Log in
Book cover

Turning up the Heat on Pain: TRPV1 Receptors in Pain and Inflammation pp 55–69Cite as

Insights into TRPV1 pharmacology provided by non-capsaicin ligands

  • Chapter

  • 820 Accesses

Part of the book series: Progress in Inflammation Research ((PIR))

This is a preview of subscription content, 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   129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   169.99
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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Appendino G, Szallasi A (1997) Euphorbium: modern research on its active principle, resiniferatoxin, revives an ancient medicine. Life Sci 60: 681–696

    Article  PubMed  CAS  Google Scholar 

  2. Adolph W, Sorg B, Hergenhahn M, Hecker E (1982) Structure-activity relations of polyfunctional diterpenes of the daphnane type I. Revised structure for resiniferatoxin and structure-activity relations for resiniferonol and some of its esters. J Nat Prod 45: 347–354

    Google Scholar 

  3. 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

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  5. Walpole CSJ, Wrigglesworth R, Bevan S, Campbell EA, Dray A, James IF, Perkins MN, Reid DJ, Winter J (1993) Analogues of capsaicin with agonist activity as novel analgesic agents: structure-activity studies. 1. The aromatic “A-region”. J Med Chem 36: 2362–2372

    PubMed  CAS  Google Scholar 

  6. Walpole CSJ, Wrigglesworth R, Bevan S, Campbell EA, Dray A, James IF, Masdin KJ, Perkins MN, Winter J (1993) Analogues of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 2. The amide bond “B-region”. J Med Chem 36: 2373–2380

    PubMed  CAS  Google Scholar 

  7. Walpole CSJ, Wrigglesworth R, Bevan S, Campbell EA, Dray A, James IF, Masdin KJ, 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

    PubMed  CAS  Google Scholar 

  8. Szolcsányi J, Jancsó-Gábor A (1975) Sensory effects of capsaicin congeners I. Relationship between chemical structure and pain-producing potency of pungent agents. Arzneim Forsch 25: 1877–1881

    Google Scholar 

  9. Janusz JM, Buckwalter BL, Young PA, LaHann TR, Farmer RW, Kasting GB, Loomans ME, Kerckaert GA, Maddin CS, Berman EF et al (1993) Vanilloids. 1. Analogs of capsaicin with antinociceptive and antiinflammatory activity. J Med Chem 36: 2595–2604

    Article  PubMed  CAS  Google Scholar 

  10. Szallasi A, Blumberg PM (1990) Specific binding of resiniferatoxin, an ultrapotent capsaicin analog, by dorsal root ganglion membranes. Brain Res 524: 106–111

    Article  PubMed  CAS  Google Scholar 

  11. Szallasi A, Lewin NE, Blumberg PM (1992) Identification of alpha1-acid glycoprotein (orosomucoid) as a major vanilloid-binding protein in serum. J Pharmacol Exp Ther 262: 883–888

    PubMed  CAS  Google Scholar 

  12. Wahl P, Foged C, Tullin S, Thomsen C (2001) Iodo-resiniferatoxin, a new potent vanilloid receptor antagonist. Mol Pharmacol 59: 9–15

    PubMed  CAS  Google Scholar 

  13. Caterina MJ, Julius D (2001) The vanilloid receptor: A molecular gateway to the pain pathway. Annu Rev Neurosci 24: 487–517

    Article  PubMed  CAS  Google Scholar 

  14. 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

    PubMed  CAS  Google Scholar 

  15. Acs G, Lee J, Marquez VE, Blumberg PM (1996) Distinct structure activity relations for stimulation of 45Ca uptake and for high affinity binding by cultured rat dorsal root ganglion neurons and dorsal root ganglion membranes. Mol Brain Res 35: 173–182

    Article  PubMed  CAS  Google Scholar 

  16. Szallasi A, Blumberg PM, Annicelli LL, Krause JE, Cortright DN (1999) The cloned rat vanilloid receptor VR1 mediates both R-type binding and C-type calcium response in dorsal root ganglion neurons. Mol Pharmacol 56: 581–587

    PubMed  CAS  Google Scholar 

  17. Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288: 306–313

    Article  PubMed  CAS  Google Scholar 

  18. Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, Overend P, Harries MH, Latcham J, Clapham C, Atkinson K et al (2000) Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405: 183–187

    Article  PubMed  CAS  Google Scholar 

  19. Appendino G, Cravotto G, Palmisano G, Annunziata R, Szallasi A (1996) Synthesis and evaluation of phorboid 20-homovanillates: discovery of a class of ligands binding to the vanilloid (capsaicin) receptor with different degrees of cooperativity. J Med Chem 39: 3123–3131

    Article  PubMed  CAS  Google Scholar 

  20. Lee J, Lee J, Kim J, Kim SY, Chun MW, Cho H, Hwang SW, Oh U, Park YH, Marquez VE et al (2001) N-(3-acyloxy-2-benzylpropyl)-N’-(4-hydroxy-3-methoxybenzyl) thiourea derivative as potent vanilloid receptor agonists and analgesics. Bioorg Med Chem 9: 19–32

    PubMed  CAS  Google Scholar 

  21. van der Stelt M, Di Marzo V (2004) Endovanilloids. Putative endogenous ligands of transient receptor potential vanilloid 1 channels. Eur J Biochem 271: 1827–1834

    Google Scholar 

  22. Pearce LV, Petukhov PA, Szabo T, Kedei N, Bizik F, Kozikowski AP, Blumberg PM (2004) Evodiamine functions as an agonist for the vanilloid receptor TRPV1. Org Biomol Chem 2: 2281–2286

    Article  PubMed  CAS  Google Scholar 

  23. Kobayashi Y (2002) The nociceptive and anti-nociceptive effects of evodiamine from fruits of Evodia rutaecarpa in mice. Planta Medica 69: 425–428

    Google Scholar 

  24. Toth A, Kedei N, Szabo T, Wang Y, Blumberg PM (2002) Thapsigargin binds to and inhibits the cloned vanilloid receptor 1. Biochem Biophys Res Commun 293: 777–782

    Article  PubMed  CAS  Google Scholar 

  25. Appendino G, Munoz E, Fiebich BL (2003) TRPV1 (vanilloid receptor, capsaicin receptor) agonists and antagonists. Expert Opin Ther Patents 13: 1825–1837

    Article  CAS  Google Scholar 

  26. Cruz F (2004) Mechanisms involved in new therapies for overactive bladder. Urology 63(suppl 3A): 65–73

    PubMed  Google Scholar 

  27. Bevan S, Hothi S, Hughes G, James IF, Rang HP, Shah K, Walpole CSJ, Yeats JC (1992) Capsazepine: a competitive antagonist of the sensory neurone excitant capsaicin. Br J Pharmacol 107: 544–552

    PubMed  CAS  Google Scholar 

  28. Wang Y, Szabo T, Welter JD, Toth A, Tran R, Lee J, Kang SU, Suh YG, Blumberg PM, Lee J (2002) High affinity antagonists of vanilloid receptor. Mol Pharmacol 62: 947–956

    Article  PubMed  CAS  Google Scholar 

  29. Valenzano KJ, Grant ER, Wu G, Hachicha M, Schmid L, Tafesse L, Sun Q, Rotshteyn Y, Francis J, Limberis J et al (2003) BCTC (N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropryazine-1(2H)-carbox-amide), a novel, orally-effective vanilloid receptor 1 antagonist with analgesic properties: I. In vitro characterization and pharmacokinetic properties. J Pharmacol Exp Ther 306: 377–386

    Article  PubMed  CAS  Google Scholar 

  30. Pomonis JD, Harrison JE, Mark L, Bristol DR. Valenzano KJ, Walker K (2003) BCTC (N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropryazine-1(2H)-carboxamide), a novel, orally-effective vanilloid receptor 1 antagonist with analgesic properties: II. In vivo characterization in rat models of inflammatory and neuropathic pain. J Pharmacol Exp Ther 306: 387–393

    Article  PubMed  CAS  Google Scholar 

  31. Lee J, Lee J, Kang M, Shin M, Kim JM, Kang SU, Lim JO, Choi HK, Suh YG, Park HG et al (2003) N-(3-acyloxy-2-benzylpropyl)-N-[4-(methylsulfonylamino)benzyl] thiourea analogues: novel potent and high affinity antagonists and partial antagonists of the vanilloid receptor. J Med Chem 46: 3116–3126

    PubMed  CAS  Google Scholar 

  32. Wang Y, Toth A, Tran R, Szabo T, Welter JD, Blumberg PM, Lee J, Kang SU, Lim JO, Lee J (2003) High affinity partial agonists of the vanilloid receptor. Mol Pharmacol 64: 325–333

    PubMed  CAS  Google Scholar 

  33. Cortright DN, Szallasi A (2004) Biochemical pharmacology of the vanilloid receptor TRPV1. An update. Eur J Biochem 271: 1814–1819

    Article  PubMed  CAS  Google Scholar 

  34. Ferrer-Montiel A, Garcia-Martinez C, Morenilla-Pallao C, Garcia-Sanz N, Fernandez-Carvajal A, Fernandez-Ballester G, Planells R (2004) Molecular architecture of the vanilloid receptor. Insights for drug design. Eur J Biochem 271: 1820–1826

    Article  PubMed  CAS  Google Scholar 

  35. Olah Z, Szabo T, Karai L, Hough C, Fields RD, Caudle RM, Blumberg PM, Iadarola MJ (2001) Ligand induced dynamic membrane changes and cell deletion conferred by vanilloid receptor 1. J Biol Chem 276: 11021–11030

    PubMed  CAS  Google Scholar 

  36. Guo A, Vulchanova L, Wang J, Li X, Elde R (1999) Immunocytochemical localization of the vanilloid receptor 1 (VR1): relationship to neuropeptides, the P2X3 purinoceptor and IB4 binding sites. J Neurosci 11:946–958

    CAS  Google Scholar 

  37. Marshall IC, Owen DE, Cripps TV, Davis JB, NcNulty S, Smart D (2003) Activation of vanilloid receptor 1 by resiniferatoxin mobilizes calcium from inositol 1,4,5-trisphosphate-sensitive stores. Br J Pharmacol 138: 172–176

    Article  PubMed  CAS  Google Scholar 

  38. Toth A, Blumberg PM, Chen Z, Kozikowski AP (2004) Design of a high affinity, competitive antagonist of the vanilloid receptor selective for the calcium entry linked receptor population. Mol Pharmacol 65: 282–291

    Article  PubMed  CAS  Google Scholar 

  39. Wrigglesworth R, Walpole CSJ, Bevan S, Campbell EA, Dray A, Hughes GA, James I, Masdin KJ, Winter J (1996) Analogues of capsaicin with agonist activity as novel analgesic agents: structure-activity studies. 4. Potent, orally active analgesics. J Med Chem 39: 4942–4951

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  41. Gavva NR, Klionsky L, Qu Y, Shi L, Tamir R, Edenson S, Zhang TJ, Vellarkad NV, Toth A, Pearce LV et al (2004) Molecular determinants of vanilloid sensitivity in TRPV1. J Biol Chem 279: 20283–20295

    Article  PubMed  CAS  Google Scholar 

  42. 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: 17165–17172

    PubMed  CAS  Google Scholar 

  43. 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

    PubMed  CAS  Google Scholar 

  44. Caterina MJ (2003) Vanilloid receptors take a TRP beyond the sensory afferent. Pain 105: 5–9

    Article  PubMed  CAS  Google Scholar 

  45. Acs G, Palkovits M, Blumberg PM (1996) Specific binding of [3H]resiniferatoxin by human and rat preoptic area, locus ceruleus, medial hypothalamus, reticular formation, and ventral thalamus membrane preparations. Life Sci 59: 1899–1908

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD, 20892, USA

    Peter M. Blumberg, Derek C. Braun, Noemi Kedei, Jozsef Lazar, Vladimir Pavlyukovets & Larry V. Pearce

Authors
  1. Peter M. Blumberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Derek C. Braun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Noemi Kedei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jozsef Lazar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vladimir Pavlyukovets
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Larry V. Pearce
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Elan Pharmaceuticals, 800 Gateway Boulevard, South San Francisco, CA, 94080, USA

    Annika B. Malmberg

  2. NeurogesX, Inc., 981F Industrial Road, San Carlos, CA, 94070, USA

    Keith R. Bley

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Birkhäuser Verlag Basel/Switzerland

About this chapter

Cite this chapter

Blumberg, P.M., Braun, D.C., Kedei, N., Lazar, J., Pavlyukovets, V., Pearce, L.V. (2005). Insights into TRPV1 pharmacology provided by non-capsaicin ligands. In: Malmberg, A.B., Bley, K.R. (eds) Turning up the Heat on Pain: TRPV1 Receptors in Pain and Inflammation. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7379-2_4

Download citation

  • DOI: https://doi.org/10.1007/3-7643-7379-2_4

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-7643-7080-0

  • Online ISBN: 978-3-7643-7379-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation