Role of prostaglandin D2 in mast cell activation-induced sensitization of esophageal vagal afferents.
Role of prostaglandin D2 in mast cell activation-induced sensitization of esophageal vagal afferents.
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前列腺素 D2 在肥大细胞激活诱导的食管迷走神经传入敏化中的作用。
DOI：
10.1152/ajpgi.00448.2012
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Yu,Shaoyong
中科院分区：
文献类型：
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作者：
Zhang,Shizhong;Grabauskas,Gintautas;Wu,Xiaoyin;Joo,MoonKyung;Heldsinger,Andrea;Song,Il;Owyang,Chung;Yu,Shaoyong
食道传入神经敏化在食道伤害性反应中起重要作用，但其机制尚不清楚。我们以前的研究表明，肥大细胞(MC)的激活释放了预先形成的介质组胺和类胰蛋白酶，它们在食道迷走神经伤害性C纤维的敏化中起着重要作用。PGD2是一种由活化的巨噬细胞释放的脂质介质。PGD2是否在这一敏化过程中起作用还有待确定。免疫荧光染色、Western blotting和RT-PCR检测结状神经节神经元中PGD2DP1和DP2受体的表达。细胞外记录在体外的食道-迷走神经准备中进行。比较PGD2、DP1和DP2受体激动剂灌流前后的食道扩张诱发的动作电位，以及在有或没有使用拮抗剂的情况下对MC的激活。应用膜片钳技术观察PGD2对1，1′-dioctadecyl-3，3，3′，3′-tetramethylindocarbocyanine高氯酸盐(DiI)标记的食管结节神经元的影响。结果表明，DP1和DP2受体的mRNA和蛋白主要在结状神经节的中小直径神经元中表达。PGD2可显著增加食道结节C纤维的动作电位放电。DP1受体激动剂BW 245C模拟这种作用。PGD2通过降低动作电位阈值直接敏化DiI标记的食道结节神经元。DP1受体拮抗剂BW A868C可显著抑制PGD2灌流或MC激活引起的食道结节C纤维动作电位放电的增加。结论：PGD2在MC激活诱导的食道结节C纤维敏化中起重要作用。这增加了内脏传入敏化的新机制。
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. PGD2is a lipid mediator released by activated MCs. Whether PGD2plays a role in this sensitization process has yet to be determined. Expression of the PGD2DP1and DP2receptors 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, DP1and DP2receptor agonists, and MC activation, with or without pretreatment with antagonists. The effect of PGD2on 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal nodose neurons was determined by patch-clamp recording. Our results demonstrate that DP1and DP2receptor mRNA and protein were expressed mainly in small- and medium-diameter neurons in nodose ganglia. PGD2significantly increased esophageal distension-evoked action potential discharges in esophageal nodose C fibers. The DP1receptor agonist BW 245C mimicked this effect. PGD2directly sensitized DiI-labeled esophageal nodose neurons by decreasing the action potential threshold. Pretreatment with the DP1receptor antagonist BW A868C significantly inhibited PGD2perfusion- or MC activation-induced increases in esophageal distension-evoked action potential discharges in esophageal nodose C fibers. In conclusion, PGD2plays an important role in MC activation-induced sensitization of esophageal nodose C fibers. This adds a novel mechanism of visceral afferent sensitization.