Evidence for the role of mast cells in colon-bladder cross organ sensitization

Jocelyn J. Fitzgerald, Elena Ustinova, Kevin B. Koronowski, William C. de Groat, Michael A. Pezzone

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6-13
Number of pages8
JournalAutonomic Neuroscience: Basic and Clinical
Volume173
Issue number1-2
DOIs
StatePublished - Jan 2013
Externally publishedYes

Keywords

  • Afferent nerves
  • Bladder
  • Bowel
  • Compound 48/80
  • Cross-sensitization
  • Mast cell
  • PAR-2
  • Trinitrobenzene sulfonic acid

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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