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ERK1/2 signaling pathway in mast cell activation-induced sensitization of esophageal nodose C-fiber neurons.
Dis Esophagus. 2011 Apr; 24(3):194-203.DE

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.

Authors+Show Affiliations

Department of Medicine, Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21073620

Citation

Gao, G, et al. "ERK1/2 Signaling Pathway in Mast Cell Activation-induced Sensitization of Esophageal Nodose C-fiber Neurons." Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus, vol. 24, no. 3, 2011, pp. 194-203.
Gao G, Ouyang A, Kaufman MP, et al. ERK1/2 signaling pathway in mast cell activation-induced sensitization of esophageal nodose C-fiber neurons. Dis Esophagus. 2011;24(3):194-203.
Gao, G., Ouyang, A., Kaufman, M. P., & Yu, S. (2011). ERK1/2 signaling pathway in mast cell activation-induced sensitization of esophageal nodose C-fiber neurons. Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus, 24(3), 194-203. https://doi.org/10.1111/j.1442-2050.2010.01127.x
Gao G, et al. ERK1/2 Signaling Pathway in Mast Cell Activation-induced Sensitization of Esophageal Nodose C-fiber Neurons. Dis Esophagus. 2011;24(3):194-203. PubMed PMID: 21073620.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ERK1/2 signaling pathway in mast cell activation-induced sensitization of esophageal nodose C-fiber neurons. AU - Gao,G, AU - Ouyang,A, AU - Kaufman,M P, AU - Yu,S, Y1 - 2010/11/12/ PY - 2010/11/16/entrez PY - 2010/11/16/pubmed PY - 2011/8/13/medline SP - 194 EP - 203 JF - Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus JO - Dis Esophagus VL - 24 IS - 3 N2 - 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. SN - 1442-2050 UR - https://www.unboundmedicine.com/medline/citation/21073620/ERK1/2_signaling_pathway_in_mast_cell_activation_induced_sensitization_of_esophageal_nodose_C_fiber_neurons_ L2 - https://academic.oup.com/dote/article-lookup/doi/10.1111/j.1442-2050.2010.01127.x DB - PRIME DP - Unbound Medicine ER -