Neurotensin mediates rat bladder mast cell degranulation triggered by acute psychological stress

Objectives, An increased number of activated mast cells have been documente d in interstitial cystitis (IC); a painful bladder disorder occurring prima rily in women and exacerbated by stress. Mast cells in the bladder and in t he intestine are often found in juxtaposition to neurons, where they are ac tivated by neuropeptides and neurotransmitters as well as by acute psycholo gical stress. This work was undertaken to investigate whether the neuropept ide neurotensin (NT) is involved in the activation of bladder mast cells by acute psychological stress. Methods. Male 300-g Sprague-Dawley rats were either kept on the bench in a quiet procedure room or stressed by confining them one at a time for 30 min utes in a clear Plexiglas immobilizer and then killed with carbon dioxide. The bladder was removed and fixed with 4% paraformaldehyde. Frozen sections were either stained with acidified toluidine blue or processed for NT immu nocytochemical analysis. An immunosorbent assay was used to also measure NT in bladder homogenate before and after stress. Results. Bladder mast cell activation in control rats was 37.3 +/- 1.4%, as judged by extrusion of granule contents. Degranulation in stressed animals increased to 75.3 +/- 5.5% (P = 0.0003). Treatment of the animals neonatal ly with capsaicin decreased mast cell degranulation to 48.9 +/- 7.5% (P = 0 .008), a 35.1% inhibition. Intraperitoneal administration of the nonpeptide NT receptor antagonist SR48692 sixty minutes before stress decreased bladd er mast cell degranulation to 25.2 +/- 3.6% (P = 0.00007), a 66.5% inhibiti on. This value is 32.5% below control levels, indicating that NT is involve d in basal mast cell degranulation. Stress also reduced the total bladder N T content. Conclusions. The present results indicate that NT mediates the effect of ac ute, nontraumatic psychological stress on bladder mast cell degranulation. They further suggest that NT receptor antagonists may be useful in subpopul ations of patients with IC in whom symptoms worsen under stress. UROLOGY 53 : 1035-1040, 1999. (C) 1999, Elsevier Science Inc. All rights reserved.