PMID- 23072452
OWN - NLM
STAT- MEDLINE
DCOM- 20130627
LR  - 20121126
IS  - 1365-2982 (Electronic)
IS  - 1350-1925 (Linking)
VI  - 24
IP  - 12
DP  - 2012 Dec
TI  - NGF is involved in oral ovalbumin-induced altered colonic contractility in rats: 
      evidence from the blockade of TrkA receptors with K252a.
PG  - e580-90
LID - 10.1111/nmo.12027 [doi]
AB  - 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.
CI  - (c) 2012 Blackwell Publishing Ltd.
FAU - Jardi, F
AU  - Jardi F
AD  - Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de 
      Barcelona, Barcelona, Spain.
FAU - Martinez, V
AU  - Martinez V
FAU - Vergara, P
AU  - Vergara P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121017
PL  - England
TA  - Neurogastroenterol Motil
JT  - Neurogastroenterology and motility
JID - 9432572
RN  - 0 (Carbazoles)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indole Alkaloids)
RN  - 9006-59-1 (Ovalbumin)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - 97161-97-2 (staurosporine aglycone)
RN  - EC 2.7.10.1 (Receptor, trkA)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Carbazoles/pharmacology
MH  - Colon/immunology/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fluorescent Antibody Technique
MH  - Gastrointestinal Motility/drug effects/*physiology
MH  - Immunohistochemistry
MH  - Indole Alkaloids/pharmacology
MH  - Intestinal Mucosa/cytology/metabolism
MH  - Male
MH  - Mast Cells/*metabolism
MH  - Nerve Growth Factor/*metabolism
MH  - Ovalbumin/immunology/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptor, trkA/*metabolism
EDAT- 2012/10/18 06:00
MHDA- 2013/06/29 06:00
CRDT- 2012/10/18 06:00
PHST- 2012/10/18 06:00 [entrez]
PHST- 2012/10/18 06:00 [pubmed]
PHST- 2013/06/29 06:00 [medline]
AID - 10.1111/nmo.12027 [doi]
PST - ppublish
SO  - Neurogastroenterol Motil. 2012 Dec;24(12):e580-90. doi: 10.1111/nmo.12027. Epub 
      2012 Oct 17.