Neurokinin-1 (NK-1) receptor is required in antigen-induced cystitis.
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.
Saban
R
R
Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, Texas, 77555-0632, USA.
Saban
M R
MR
Nguyen
N B
NB
Lu
B
B
Gerard
C
C
Gerard
N P
NP
Hammond
T G
TG
D000818:Animals; D015550:Cell Degranulation / Q000276:immunology; D018856:Cystitis, Interstitial / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D004136:Dinitrobenzenes / Q000008:administration & dosage; D004140:Dinitrophenols / Q000008:administration & dosage; D005260:Female; D006969:Hypersensitivity, Immediate / Q000209:etiology / Q000473:pathology; D007114:Immunization; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage; D018040:Receptors, Neurokinin-1 / Q000172:deficiency / Q000502:physiology*; D013373:Substance P / Q000502:physiology; D001743:Urinary Bladder / Q000473:pathology
D004136:Dinitrobenzenes; D004140:Dinitrophenols; D018040:Receptors, Neurokinin-1; C045521:dinitrophenol-ovalbumin; D013373:Substance P; D010047:Ovalbumin