ERK1/2 signaling pathway in mast cell activation-induced sensitization of esophageal nodose C-fiber neurons

G. Gao, A. Ouyang, Marc P Kaufman, S. Yu

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Sensitization of esophageal nociceptive afferents by inflammatory mediators plays an important role in esophageal inflammatory nociception. Our previous studies demonstrated that esophageal mast cell activation increases the excitability of esophageal nodose C-fibers. But the intracellular mechanism of this sensitization process is still less clear. We hypothesize that extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathway plays an important role in mast cell activation-induced sensitization of esophageal nodose C-fiber neurons. Mast cell activation and in vivo esophageal distension-induced phosphorylations of ERK1/2 were studied by immuno-staining and Western blot in esophageal nodose neurons. Extracellular recordings were performed from nodose neurons using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Nerve excitabilities were compared by action potentials evoked by esophageal distensions before and after mast cell activations with/without pretreatment of mitogen-activated protein kinases (MAPK)/ERK kinase inhibitor U0126. The expressions of phospho-ERK1/2 (p-ERK1/2) in the same nodose ganglia were then studied by Western blot. Mast cell activation enhances in vivo esophageal distension-induced phosphorylation of ERK1/2 in nodose neurons. This can be prevented by pretreatment with mast cell stabilizer cromolyn. In ex vivo esophageal-vagal preparations, both mast cell activation and proteinase-activated receptor 2 (PAR2)-activating peptide perfusion increases esophageal distension-induced mechano-excitability of esophageal nodose C-fibers and phosphorylation of ERK1/2 in nodose neurons. Pretreatment with MAPK/ERK kinase inhibitor U0126 prevents these potentiation effects. Collectively, our data demonstrated that mast cell activation enhances esophageal distension-induced mechano-excitability and phosphorylation of ERK1/2 in esophageal nodose C-fiber neurons. This reveals a new intracellular pathway of esophageal peripheral sensitization and inflammatory nociception.

Original languageEnglish (US)
Pages (from-to)194-203
Number of pages10
JournalDiseases of the Esophagus
Volume24
Issue number3
DOIs
StatePublished - Apr 2011
Externally publishedYes

Fingerprint

Unmyelinated Nerve Fibers
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Mast Cells
Neurons
Phosphorylation
Nociception
Mitogen-Activated Protein Kinase Kinases
Western Blotting
Nodose Ganglion
PAR-2 Receptor
Cromolyn Sodium
Nerve Endings
Esophagus
Action Potentials
Perfusion
Staining and Labeling
Peptides

Keywords

  • ERK1/2
  • Esophagus
  • Mast cell
  • Nodose
  • Sensory afferent

ASJC Scopus subject areas

  • Gastroenterology

Cite this

ERK1/2 signaling pathway in mast cell activation-induced sensitization of esophageal nodose C-fiber neurons. / Gao, G.; Ouyang, A.; Kaufman, Marc P; Yu, S.

In: Diseases of the Esophagus, Vol. 24, No. 3, 04.2011, p. 194-203.

Research output: Contribution to journalArticle

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