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The Role of Mast Cells and Protease Activated Receptors, Type‐2 (PAR‐2R) in Pelvic Afferent Cross‐ Sensitization
Author(s) -
Fitzgerald Jocelyn J,
Groat William C,
Ustinova Elena,
Pezzone Michael A
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1120.1
Subject(s) - capsaicin , sensitization , agonist , mast cell , chemistry , receptor , medicine , endocrinology , substance p , pharmacology , immunology , neuropeptide
Colitis induced in rats by trinitrobenzenesulfonic acid (TNBS) causes cross‐sensitization (C‐S) of the urinary bladder (UB) as evidenced by increased void frequency. This study examined the role of mast cells (MCs) in this type of C‐S. 7–12 days after intracolonic TNBS in female rats, PAR‐2R expression, voiding interval (VI), urothelial permeability (UTP), afferent nerve firing (ANF) and muscle strip contractility (MSC) were measured. In TNBS, cystometric VIs decreased from 287 ± 41s/sec in controls to 181 ± 8 s/sec in TNBS (p=0.015), and ANF induced by capsaicin or UB distension was enhanced 2–3 fold (p<0.05). These effects were abolished by pre‐treatment with Ketotifen, a MC stabilizing agent (10 mg/kg/day for 5 days in the drinking water). This agent did not reverse UB mastocytosis but normalized UTP measured by fluorescein uptake which increased from 0.99 ± 0.22 ug/ml of plasma in controls to 3.01 ± 0.64 ug/ml in TNBS (p=0.012). In TNBS, PAR‐2R immunoreactivity increased in the UT, and the facilitatory effect of a PAR‐2R agonist (SLIGRL) on UB capsaicin‐sensitive afferents significantly increased two fold. MSC induced by 48/80 (50μg/ml), a MC stimulating agent and SLIGRL (100 μM) was enhanced in TNBS. These data indicate that UB dysfunction in the TNBS‐induced, C‐S model is mediated by increased release of inflammatory mediators from MCs that enhance sensory mechanisms in the UB. Support: NIH R01 DK066658 and DK49430