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

Alexacos N, Pang X, Boucher W, Cochrane DE, Sant GR, Theoharides
TC

Department of Pharmacology and Experimental Therapeutics, Tufts
University School of Medicine, New England Medical Center,
Boston, Massachusetts 02111, USA.

[Medline record in process]

OBJECTIVES: An increased number of activated mast cells have
been documented in interstitial cystitis (IC), a painful bladder
disorder occurring primarily in women and exacerbated by stress.
Mast cells in the bladder and in the intestine are often found
in juxtaposition to neurons, where they are activated by
neuropeptides and neurotransmitters as well as by acute
psychological stress. This work was undertaken to investigate
whether the neuropeptide 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 minutes 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
immunocytochemical 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 neonatally 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 bladder mast cell degranulation to 25.2 +/-
3.6% (P = 0.00007), a 66.5% inhibition. This value is 32.5%
below control levels, indicating that NT is involved in basal
mast cell degranulation. Stress also reduced the total bladder
NT content. CONCLUSIONS: The present results indicate that NT
mediates the effect of acute, nontraumatic psychological stress
on bladder mast cell degranulation. They further suggest that NT
receptor antagonists may be useful in subpopulations of patients
with IC in whom symptoms worsen under stress