Evidence for the role of mast cells in colon-bladder cross organ sensitization
| Autor: | Jocelyn J. Fitzgerald, William C. de Groat, Elena E. Ustinova, Michael A. Pezzone, Kevin B. Koronowski |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Ketotifen
medicine.medical_specialty Colon Urinary Bladder Permeability Article Rats Sprague-Dawley Cellular and Molecular Neuroscience chemistry.chemical_compound Mice Oral administration Internal medicine Membrane Transport Modulators medicine Animals Receptor PAR-2 p-Methoxy-N-methylphenethylamine Mast Cells Neurons Afferent Receptor Sensitization Mice Knockout Urinary bladder Endocrine and Autonomic Systems Urination disorder Compound 48/80 Mast cell Colitis Urination Disorders Rats Disease Models Animal Proto-Oncogene Proteins c-kit medicine.anatomical_structure Endocrinology chemistry Trinitrobenzenesulfonic Acid Immunology Female Neurology (clinical) Oligopeptides medicine.drug Muscle Contraction |
| Zdroj: | Autonomic neuroscience : basicclinical. 173(1-2) |
| ISSN: | 1872-7484 |
| Popis: | This study examined the contribution of mast cells to colon-bladder cross organ sensitization induced by colon irritation with trinitrobenzene sulfonic acid (TNBS-CI). In urethane anesthetized rats 12 days after TNBS-CI, the voiding interval was reduced from 357 s to 201 s and urothelial permeability, measured indirectly by absorption of sodium fluorescein from the bladder lumen, increased six-fold. These effects were blocked by oral administration of ketotifen (10 mg/kg, for 5 days), a mast cell stabilizing agent. TNBS-CI in wild type mice produced a similar decrease in voiding interval (from 319 s to 209 s) and a 10-fold increase in urothelial permeability; however this did not occur in KitaWa/KitaW-va mast cell deficient mice. Contractile responses of bladder strips elicited by Compound 48/80 (50 μg/ml), a mast cell activating agent, were significantly larger in strips from rats with TNBS-CI (145% increase in baseline tension) than in control rats (55% increase). The contractions of strips from rats with TNBS-CI were reduced 80-90% by pretreatment of strips with ketotifen (20 μM), whereas contractions of strips from control animals were not significantly changed. Bladder strips were pretreated with SLIGRL-NH2 (100 μM) to desensitize PAR-2, the receptor for mast cell tryptase. SLIGRL-NH2 pretreatment reduced by 60-80% the 48/80 induced contractions in strips from rats with TNBS-CI but did not alter the contractions in strips from control rats. These data indicate that bladder mast cells contribute to the bladder dysfunction following colon-bladder cross-sensitization. |
| Databáze: | OpenAIRE |
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