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Role of prostaglandin D2 in mast cell activation-induced sensitization of esophageal vagal afferents.
Am J Physiol Gastrointest Liver Physiol. 2013 May 15; 304(10):G908-16.AJ

Abstract

Sensitization of esophageal afferents plays an important role in esophageal nociception, but the mechanism is less clear. Our previous studies demonstrated that mast cell (MC) activation releases the preformed mediators histamine and tryptase, which play important roles in sensitization of esophageal vagal nociceptive C fibers. PGD2 is a lipid mediator released by activated MCs. Whether PGD2 plays a role in this sensitization process has yet to be determined. Expression of the PGD2 DP1 and DP2 receptors in nodose ganglion neurons was determined by immunofluorescence staining, Western blotting, and RT-PCR. Extracellular recordings were performed in ex vivo esophageal-vagal preparations. Action potentials evoked by esophageal distension were compared before and after perfusion of PGD2, DP1 and DP2 receptor agonists, and MC activation, with or without pretreatment with antagonists. The effect of PGD2 on 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal nodose neurons was determined by patch-clamp recording. Our results demonstrate that DP1 and DP2 receptor mRNA and protein were expressed mainly in small- and medium-diameter neurons in nodose ganglia. PGD2 significantly increased esophageal distension-evoked action potential discharges in esophageal nodose C fibers. The DP1 receptor agonist BW 245C mimicked this effect. PGD2 directly sensitized DiI-labeled esophageal nodose neurons by decreasing the action potential threshold. Pretreatment with the DP1 receptor antagonist BW A868C significantly inhibited PGD2 perfusion- or MC activation-induced increases in esophageal distension-evoked action potential discharges in esophageal nodose C fibers. In conclusion, PGD2 plays an important role in MC activation-induced sensitization of esophageal nodose C fibers. This adds a novel mechanism of visceral afferent sensitization.

Authors+Show Affiliations

Division of Gastroenterology, Dept. of Medicine, Univ. of Michigan Medical School, Ann Arbor, MI 48105, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

23471341

Citation

Zhang, Shizhong, et al. "Role of Prostaglandin D2 in Mast Cell Activation-induced Sensitization of Esophageal Vagal Afferents." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 304, no. 10, 2013, pp. G908-16.
Zhang S, Grabauskas G, Wu X, et al. Role of prostaglandin D2 in mast cell activation-induced sensitization of esophageal vagal afferents. Am J Physiol Gastrointest Liver Physiol. 2013;304(10):G908-16.
Zhang, S., Grabauskas, G., Wu, X., Joo, M. K., Heldsinger, A., Song, I., Owyang, C., & Yu, S. (2013). Role of prostaglandin D2 in mast cell activation-induced sensitization of esophageal vagal afferents. American Journal of Physiology. Gastrointestinal and Liver Physiology, 304(10), G908-16. https://doi.org/10.1152/ajpgi.00448.2012
Zhang S, et al. Role of Prostaglandin D2 in Mast Cell Activation-induced Sensitization of Esophageal Vagal Afferents. Am J Physiol Gastrointest Liver Physiol. 2013 May 15;304(10):G908-16. PubMed PMID: 23471341.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of prostaglandin D2 in mast cell activation-induced sensitization of esophageal vagal afferents. AU - Zhang,Shizhong, AU - Grabauskas,Gintautas, AU - Wu,Xiaoyin, AU - Joo,Moon Kyung, AU - Heldsinger,Andrea, AU - Song,Il, AU - Owyang,Chung, AU - Yu,Shaoyong, Y1 - 2013/03/07/ PY - 2013/3/9/entrez PY - 2013/3/9/pubmed PY - 2013/7/19/medline KW - C fiber KW - PGD2 KW - esophagus KW - mast cell KW - vagal afferent SP - G908 EP - 16 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 304 IS - 10 N2 - Sensitization of esophageal afferents plays an important role in esophageal nociception, but the mechanism is less clear. Our previous studies demonstrated that mast cell (MC) activation releases the preformed mediators histamine and tryptase, which play important roles in sensitization of esophageal vagal nociceptive C fibers. PGD2 is a lipid mediator released by activated MCs. Whether PGD2 plays a role in this sensitization process has yet to be determined. Expression of the PGD2 DP1 and DP2 receptors in nodose ganglion neurons was determined by immunofluorescence staining, Western blotting, and RT-PCR. Extracellular recordings were performed in ex vivo esophageal-vagal preparations. Action potentials evoked by esophageal distension were compared before and after perfusion of PGD2, DP1 and DP2 receptor agonists, and MC activation, with or without pretreatment with antagonists. The effect of PGD2 on 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal nodose neurons was determined by patch-clamp recording. Our results demonstrate that DP1 and DP2 receptor mRNA and protein were expressed mainly in small- and medium-diameter neurons in nodose ganglia. PGD2 significantly increased esophageal distension-evoked action potential discharges in esophageal nodose C fibers. The DP1 receptor agonist BW 245C mimicked this effect. PGD2 directly sensitized DiI-labeled esophageal nodose neurons by decreasing the action potential threshold. Pretreatment with the DP1 receptor antagonist BW A868C significantly inhibited PGD2 perfusion- or MC activation-induced increases in esophageal distension-evoked action potential discharges in esophageal nodose C fibers. In conclusion, PGD2 plays an important role in MC activation-induced sensitization of esophageal nodose C fibers. This adds a novel mechanism of visceral afferent sensitization. SN - 1522-1547 UR - https://www.unboundmedicine.com/medline/citation/23471341/Role_of_prostaglandin_D2_in_mast_cell_activation_induced_sensitization_of_esophageal_vagal_afferents_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00448.2012?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -