Monochloramine effects on gallbladder contractility

Digestive inflammatory processes induce motility alterations associated with an increase in reactive oxygen species production, including monochloramine (NH2Cl). The aim of the study was to characterize the effects of the naturally occurring oxidant monochloramine in the guinea pig gallbladder. We used standard in vitro contractility technique to record guinea pig gallbladder strips contractions. NH2Cl caused a concentration‐dependent contraction which was reduced by inhibition of extracellular Ca2+ influx and tyrosine kinase pathways. The PKC antagonist GF109203X also reduced the response but not after previous tyrosine kinase inhibition, suggesting that PKC is activated by tyrosine kinase activity. The NH2Cl contractile effect was also reduced by inhibitors of mitogen‐activated protein kinase (MAPK), nitric oxide synthase, phospholipase A2 and cyclooxygenase. In addition, NH2Cl impaired the responses to CCK, tissue depolarization and electrical field stimulation. In conclusion, we present new evidence that monochloramine impairs not only the gallbladder response to CCK but also to membrane depolarization and nervous plexus stimulation, and that tyrosine kinase, PKC, MAPK and NO pathways are involved in the contractile direct effect of monochloramine. The neutrophil‐derived oxidant monochloramine (NH2Cl) impairs the gallbladder contractile response to physiological agonists (nervous plexus, the gut hormone CCK and opening of voltage‐operated Ca2+ channels). In addition, NH2Cl contracts gallbladder muscle activating Tyr kinase‐dependent pathways and prostaglandin and NO pro‐contractile pathways.