NGF is involved in oral ovalbumin-induced altered colonic contractility in rats: Evidence from the blockade of TrkA receptors with K252a

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Abstract

Background Nerve growth factor (NGF)-mucosal mast cell (MMC) interaction has been implicated in the remodeling of enteric circuitries and associated functional changes. We investigated the involvement of NGF and its receptor TrkA in the altered colonic contractile activity observed in the model of oral ovalbumin (OVA)-induced MMC hyperactivity in rats. We also studied the role of colonic MMCs as a source of NGF. Methods Rats received oral OVA, alone or with the TrkA antagonist K252a. Colonic co-expression of NGF/TrkA and rat mast cell protease II (RMCPII) (double immunofluorescence), RMCPII content (ELISA) and expression of NGF, Brain-derived neurotrophic factor (BDNF) and TrkA/B (QT-PCR) were assessed. Colonic contractile activity was determined in vivo and in vitro. Key Results TrkA, but not NGF, was localized in colonic MMCs (RMCPII-positive). Oral ovalbumin exposure increased colonic RMCPII levels but did not change the percentage of TrkA-positive MMCs. Neither OVA nor K252a, alone or combined, altered NGF, BDNF or TrkA/B expression. Spontaneous colonic activity in vivo and in vitro was altered by OVA, an effect prevented by K252a. Electrical stimulation-induced contractile responses in vivo and carbachol responses in vitro were increased by OVA in a K252a-independent manner. In OVA-treated animals, inhibition of NO synthesis with l-NNA significantly enhanced spontaneous colonic activity in vitro, a response completely prevented by K252a. Conclusions & Inferences These results suggest that NGF-TrkA-dependent pathways are implicated in colonic contractile alterations observed during OVA exposure in rats. NGF-TrkA system might represent a potential target for treatment of gastrointestinal disorders characterized by colonic motor alterations. © 2012 Blackwell Publishing Ltd.
Original languageEnglish
JournalNeurogastroenterology and Motility
Volume24
DOIs
Publication statusPublished - 1 Dec 2012

Keywords

  • Colonic contractility
  • K252a
  • Mucosal mast cells
  • Nerve growth factor
  • Ovalbumin
  • TrkA

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