The role of Mrgprs in substance P-induced itch

Mrgprs 在 P 物质引起的瘙痒中的作用

• 批准号: 8997980
• 负责人: Ethan A Lerner
• 金额: $ 18.52万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8997980
• 关键词: Action Potentials; Afferent Neurons; Agonist; Antihistamines; Behavior; Cations; Chemicals; Cholestasis; Chronic; Cluster Analysis; Computer Simulation; Cutaneous; Data; Disease; Effectiveness; Fabaceae; Family; Fiber; G-Protein-Coupled Receptors; Gene Cluster; Generations; Genes; Genetic; Health; Histamine; Human; In Vitro; Inflammation; Injection of therapeutic agent; Kidney Failure; Knock-out; Knockout Mice; Lead; Ligand Binding; Ligands; Link; Mediating; Mediator of activation protein; Mus; Neurogenic Inflammation; Neurons; Neuropeptides; Nociception; Nociceptors; PAR-2 Receptor; Pain; Peptide Hydrolases; Peptides; Pharmaceutical Preparations; Play; Pruritus; Quality of life; Role; Sensory; Signal Pathway; Signal Transduction; Skin; Substance P; Substance P Receptor; TRPV1 gene; TSLP gene; Testing; Work; base; behavioral study; cytokine; in vivo; insight; keratinocyte; knock-down; member; novel therapeutics; receptor; research study; response; seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; skin disorder; therapeutic target; tool

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.

描述（由申请人提供）：P 物质在瘙痒和神经源性炎症中发挥关键作用。这种神经肽被认为是通过 NK1 受体介导其作用。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，它们是 Mrgpr 受体家族的同源成员，与瘙痒和伤害感受密切相关。在 Mrg 敲除小鼠中，SP 诱发的抓挠减少至基线。我们假设人类 MrgprX2 和小鼠 MrgprA1 在 SP 引起的瘙痒中发挥关键作用。评估这一假设有可能带来变革，为理解瘙痒的基本机制提供新的见解，同时确定治疗靶点，从而为瘙痒患者开发新的药物。