多不饱和脂肪酸在IBS中的作用机制
创作:aluba 审核:aluba 2019年01月04日
  • IBS患者体内的多不饱和脂肪酸(PUFA)代谢产物丰度增加;
  • 结肠活检样本的质谱分析显示,便秘型IBS(IBS-C)患者的5-oxoeicosatetraenoic酸(5-oxoETE)丰度升高;
  • 5-oxoETE在小鼠体内可引起躯体和内脏对机械刺激的高敏感性,且不引起组织炎症;
  • 5-oxoETE可直接作用于人及小鼠的感觉神经元,通过磷脂酶C及百日咳毒素依赖性机制,选择性地刺激非肽能的同工凝集素B4阳性的背根神经节神经元,提示5-oxoETE通过GPCR刺激神经元。
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aluba
Science Signaling上发表的一项最新研究,对一种在便秘型IBS患者的结肠中丰度较高的多不饱和脂肪酸——5-oxoETE的作用机制进行了分析,发现5-oxoETE可通过GPCR刺激神经元,引起机体对机械刺激的高敏感性,提示5-oxoETE在便秘型IBS患者的腹痛中起到的关键作用。
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Science Signaling [IF:8.192]

5-oxoETE triggers nociception in constipation-predominant irritable bowel syndrome through MAS-related G protein-coupled receptor D

5-oxoETE通过MAS相关G蛋白偶联受体触发便秘型IBS患者的伤害感受

10.1126/scisignal.aal2171

2018-12-18, Article

Abstract & Authors:展开

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Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is characterized by chronic abdominal pain concurrent with altered bowel habit. Polyunsaturated fatty acid (PUFA) metabolites are increased in abundance in IBS and are implicated in the alteration of sensation to mechanical stimuli, which is defined as visceral hypersensitivity. We sought to quantify PUFA metabolites in patients with IBS and evaluate their role in pain. Quantification of PUFA metabolites by mass spectrometry in colonic biopsies showed an increased abundance of 5-oxoeicosatetraenoic acid (5-oxoETE) only in biopsies taken from patients with IBS with predominant constipation (IBS-C). Local administration of 5-oxoETE to mice induced somatic and visceral hypersensitivity to mechanical stimuli without causing tissue inflammation. We found that 5-oxoETE directly acted on both human and mouse sensory neurons as shown by lumbar splanchnic nerve recordings and Ca imaging of dorsal root ganglion (DRG) neurons. We showed that 5-oxoETE selectively stimulated nonpeptidergic, isolectin B4 (IB4)-positive DRG neurons through a phospholipase C (PLC)- and pertussis toxin-dependent mechanism, suggesting that the effect was mediated by a G protein-coupled receptor (GPCR). The MAS-related GPCR D (Mrgprd) was found in mouse colonic DRG afferents and was identified as being implicated in the noxious effects of 5-oxoETE. Together, these data suggest that 5-oxoETE, a potential biomarker of IBS-C, induces somatic and visceral hyperalgesia without inflammation in an Mrgprd-dependent manner. Thus, 5-oxoETE may play a pivotal role in the abdominal pain associated with IBS-C.

First Authors:
Tereza Bautzova,James R F Hockley,Teresa Perez-Berezo

Correspondence Authors:
Nicolas Cenac

All Authors:
Tereza Bautzova,James R F Hockley,Teresa Perez-Berezo,Julien Pujo,Michael M Tranter,Cleo Desormeaux,Maria Raffaella Barbaro,Lilian Basso,Pauline Le Faouder,Corinne Rolland,Pascale Malapert,Aziz Moqrich,Helene Eutamene,Alexandre Denadai-Souza,Nathalie Vergnolle,Ewan St John Smith,David I Hughes,Giovanni Barbara,Gilles Dietrich,David C Bulmer,Nicolas Cenac

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