The Journal of Urology
Volume 181, Issue 1 , Pages 379-386 , January 2009

GRC-6211, a New Oral Specific TRPV1 Antagonist, Decreases Bladder Overactivity and Noxious Bladder Input in Cystitis Animal Models

  • Ana Charrua

      Affiliations

    • Universidade do Porto, Porto, Portugal
    • ,
  • Célia D. Cruz

      Affiliations

    • Universidade do Porto, Porto, Portugal
    • ,
  • Shridhar Narayanan

      Affiliations

    • Department of Biological Research, Glenmark Pharmaceuticals, Ltd., Navi Mumbai, India
    • Financial interest and/or other relationship with Glenmark Pharmaceutical.
    • ,
  • Laxmikant Gharat

      Affiliations

    • Department of Discovery Chemistry, Glenmark Pharmaceuticals, Ltd., Navi Mumbai, India
    • Financial interest and/or other relationship with Glenmark Pharmaceutical.
    • ,
  • Srinivas Gullapalli

      Affiliations

    • Department of Biological Research, Glenmark Pharmaceuticals, Ltd., Navi Mumbai, India
    • Financial interest and/or other relationship with Glenmark Pharmaceutical.
    • ,
  • Francisco Cruz

      Affiliations

    • Institute of Histology and Embryology, Faculty of Medicine and Instituto de Biologia Molecular e Celular, Porto, Portugal
    • Department of Urology, Hospital de São João, Porto, Portugal
    • ,
  • António Avelino

      Affiliations

    • Universidade do Porto, Porto, Portugal
    • Corresponding Author InformationCorrespondence: Institute of Histology and Embryology, Faculty of Medicine of Porto, Universidade do Porto, Porto, Portugal (FAX: 225513655)

Received 2 April 2008

References 

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  3. Avelino A, Cruz F. TRPV1 (vanilloid receptor) in the urinary tract: expression, function and clinical applications. Naunyn-Schmied Arch Pharmacol. 2006;373:287
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  8. Jordt SE, Tominaga M, Julius D. Acid potentiation of the capsaicin receptor determined by a key extracellular site. Proc Natl Acad Sci U S A. 2000;97:8134
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  12. Morenilla-Palao C, Planells-Cases R, Garcia-Sanz N, Ferrer-Montiel A. Regulated exocytosis contributes to protein kinase C potentiation of vanilloid receptor activity. J Biol Chem. 2004;279:25665
  13. Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, et al. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science. 2000;288:306
  14. Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, Overend P, et al. Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature. 2000;405:183
  15. Cockayne DA, Hamilton SG, Zhu QM, Dunn PM, Zhong Y, Novakovic S, et al. Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice. Nature. 2000;407:1011
  16. Jones RC, Xu L, Gebhart GF. 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. 2005;25:10981
  17. Feng NH, Lee HH, Shianh JC, Ma MC. Transient receptor potential vanilloid type 1 channels act as mechanoreceptors and cause substance P release and sensory activation in rat kidneys. Am J Physiol Renal Physiol. 2008;294:F316
  18. Liu L, Mansfield KJ, Kristiana I, Vaux KJ, Millard RJ, Burcher E. The molecular basis of urgency: regional difference of vanilloid receptor expression in the human urinary bladder. Neurourol Urodyn. 2007;26:433
  19. Smet PJ, Moore KH, Jonavicius J. Distribution and colocalization of calcitonin gene-related peptide, tachykinins and vasoactive intestinal peptide in normal and idiopathic unstable human urinary bladder. Lab Invest. 1997;77:37
  20. Brady CM, Apostolidis AN, Harper M, Yiangou Y, Beckett A, Jacques TS, et al. Parallel changes in bladder suburothelial vanilloid receptor TRPV1 and pan-neuronal marker PGP9.5 immunoreactivity in patients with neurogenic detrusor overactivity after intravesical resiniferatoxin treatment. BJU Int. 2004;93:770
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 Study was performed according to the European Communities Council Directive of 24 November 1986 (86/609/EEC).

 Supported by POCI/SAU-NEU/55983/2004 from FCT, Portugal and Glenmark Pharmaceuticals, Ltd., India.

PII: S0022-5347(08)02413-0

doi: 10.1016/j.juro.2008.08.121

The Journal of Urology
Volume 181, Issue 1 , Pages 379-386 , January 2009

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