title: Evidence for the role of mast cells in colon-bladder cross organ sensitization.
abstract: 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.
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15260, USA. jocelynfitzgerald@gmail.com
authors.forename: Jocelyn J
authors.initials: JJ
authors.lastname: Fitzgerald
authors.forename: Elena
authors.initials: E
authors.lastname: Ustinova
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Koronowski
authors.forename: William C
authors.initials: WC
authors.lastname: de Groat
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pezzone
mesh_terms: D000818:Animals; D003092:Colitis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D003106:Colon / Q000187:drug effects / Q000276:immunology* / Q000294:innervation; D004195:Disease Models, Animal; D005260:Female; D007665:Ketotifen / Q000494:pharmacology / Q000627:therapeutic use; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D049990:Membrane Transport Modulators / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044464:Receptor, PAR-2 / Q000819:agonists / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid; D001743:Urinary Bladder / Q000276:immunology* / Q000294:innervation / Q000378:metabolism / Q000503:physiopathology; D014555:Urination Disorders / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D049990:Membrane Transport Modulators; D009842:Oligopeptides; D044464:Receptor, PAR-2; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D003189:p-Methoxy-N-methylphenethylamine; D014302:Trinitrobenzenesulfonic Acid; D019009:Proto-Oncogene Proteins c-kit; D007665:Ketotifen