The role of Mrgprs in substance P-induced itch

描述(申请人提供)：P物质在瘙痒和神经源性炎症中起关键作用。这种神经肽被认为是通过NK1受体介导其活动的。出乎意料的是，我们发现P物质是人类MRgX2和小鼠MRgA1的有效激动剂，这两个受体是与瘙痒和伤害性感受密切相关的MRgPR家族的同源成员。在MRG基因敲除小鼠中，SP诱发的抓挠反应减少到基线水平。我们推测人和小鼠的mRgprX2和mRgprA1在SP诱导的瘙痒中起关键作用。评估这一假说具有潜在的变革性，它为理解瘙痒的基本机制提供了新的见解，同时确定了治疗目标，从而为那些遭受瘙痒折磨的人提供了新的药物。

DESCRIPTION (provided by applicant): Substance P plays critical roles in itch and neurogenic inflammation. This neuropeptide has been thought to mediate its actions via the NK1 receptor. Unexpectedly, we have found that substance P is a potent agonist of human MrgX2 and mouse MrgA1, homologous members of the Mrgpr family of receptors that been linked strongly to itch and nociception. SP-evoked scratching is reduced to baseline in Mrg knockout mice. We hypothesize that human MrgprX2 and mouse MrgprA1 play critical roles in SP-induced itch. Evaluating this hypothesis has the potential to be transformative by providing new insights into understanding the basic mechanisms of itch while identifying therapeutic targets leading to new medications for those who suffer from itch.