Neurokinin-1 (NK-1) receptor is required in antigen-induced cystitis.

Journal Article (Journal Article)

Interstitial cystitis (IC) is a debilitating disease that has been adversely affecting the quality of women's lives for many years. The trigger in IC is not entirely known, and a role for the sensory nerves in its pathogenesis has been suggested. In addition to inflammation, increased mast cell numbers in the detrusor muscle have been reported in a subset of IC patients. Experimentally, several lines of evidence support a central role for substance P and neurokinin-1 (NK-1) receptors in cystitis. The availability of mice genetically deficient in neurokinin-1 receptor (NK-1R(-/-)) allows us to directly evaluate the importance of substance P in cystitis. An unexpected finding of this investigation is that NK-1R(-/-) mice present increased numbers of mast cells in the bladder when compared with wild-type control mice. Despite the increase in mast cell numbers, no concomitant inflammation was observed. In addition, bladder instillation of wild-type mice with a sensitizing antigen induces activation of mast cells and an acute inflammatory response characterized by plasma extravasation, edema, and migration of neutrophils. Antigen-sensitized NK-1R(-/-) mice also exhibit bladder mast cell degranulation in response to antigen challenge. However, NK-1R(-/-) mice are protected from inflammation, failing to present bladder inflammatory cell infiltrate or edema in response to antigen challenge. This work presents the first evidence of participation of NK-1 receptors in cystitis and a mandatory participation of these receptors on the chain of events linking mast cell degranulation and inflammation.

Full Text

Duke Authors

Cited Authors

  • Saban, R; Saban, MR; Nguyen, NB; Lu, B; Gerard, C; Gerard, NP; Hammond, TG

Published Date

  • March 2000

Published In

Volume / Issue

  • 156 / 3

Start / End Page

  • 775 - 780

PubMed ID

  • 10702392

Pubmed Central ID

  • PMC1876835

International Standard Serial Number (ISSN)

  • 0002-9440

Digital Object Identifier (DOI)

  • 10.1016/S0002-9440(10)64944-9


  • eng

Conference Location

  • United States