个性化检查点针灸可以减轻腹部手术后的疼痛——一项符合STRICTA的初步研究

WTW

Personalized checkpoint acupuncture can reduce postoperative pain after abdominal surgery-a STRICTA-conform pilot study
个性化检查点针灸可以减轻腹部手术后的疼痛——一项符合STRICTA的初步研究
Abstract

Mas-related G protein-coupled receptor-X2 (MRGPRX2) is known as a novel receptor to activate mast cells (MCs). MRGPRX2 plays a dual role in promoting MC-dependent host defense and immunomodulation and contributing to the pathogenesis of pseudo-allergic drug reactions, pain, itching, and inflammatory diseases. In this article, we discuss the possible signaling pathways of MCs activation mediated by MRGPRX2 and summarize and classify agonists and inhibitors of MRGPRX2 in MCs activation. MRGPRX2 is a low-affinity and low-selectivity receptor, which allows it to interact with a diverse group of ligands. Diverse MRGPRX2 ligands utilize conserved residues in its transmembrane (TM) domains and carboxyl-terminus Ser/Thr residues to undergo ligand binding and G protein coupling. The coupling likely initiates phosphorylation cascades, induces Ca2+ mobilization, and causes degranulation and generation of cytokines and chemokines via MAPK and NF-κB pathways, resulting in MCs activation. Agonists of MRGPRX2 on MCs are divided into peptides (including antimicrobial peptides, neuropeptides, MC degranulating peptides, peptide hormones) and nonpeptides (including FDA-approved drugs). Inhibitors of MRGPRX2 include non-selective GPCR inhibitors, herbal extracts, small-molecule MRGPRX2 antagonists, and DNA aptamer drugs. Screening and classifying MRGPRX2 ligands and summarizing their signaling pathways would improve our understanding of MRGPRX2-mediated physiological and pathological effects on MCs.

Keywords: Agonist; Antagonist; Degranulation; Generation of cytokines and chemokines; Host defense; Inflammatory diseases; Inhibitors; Mas-related G protein-coupled receptor-X2; Mast cells; Pseudo-allergic drug reactions.

摘要Mas相关G蛋白偶联受体X2（MRGPRX2）是一种新的激活肥大细胞（MC）的受体。MRGPRX2在促进MC依赖性宿主防御和免疫调节方面发挥双重作用，并参与伪过敏性药物反应、疼痛、瘙痒和炎症性疾病的发病机制。在这篇文章中，我们讨论了MRGPRX2介导的MCs激活的可能信号通路，并总结和分类了MRGPRS2在MCs激活中的激动剂和抑制剂。MRGPRX2是一种低亲和力和低选择性受体，使其能够与多种配体相互作用。多种MRGPRX2配体利用其跨膜（TM）结构域中的保守残基和羧基末端Ser/Thr残基进行配体结合和G蛋白偶联。这种偶联可能启动磷酸化级联反应，诱导Ca2+动员，并通过MAPK和NF-κB途径引起脱颗粒和细胞因子和趋化因子的产生，从而导致MCs活化。MCs上MRGPRX2的激动剂分为肽（包括抗菌肽、神经肽、MC脱颗粒肽、肽激素）和非肽（包括FDA批准的药物）。MRGPRX2的抑制剂包括非选择性GPCR抑制剂、草药提取物、小分子MRGPRF2拮抗剂和DNA适体药物。筛选和分类MRGPRX2配体并总结它们的信号通路将提高我们对MRGPRX2-介导的MCs的生理和病理影响的理解。关键词：激动剂；敌手脱颗粒；细胞因子和趋化因子的产生；宿主防御；炎症性疾病；抑制剂；Mas相关G蛋白偶联受体X2；肥大细胞；伪过敏性药物反应。

https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/37814175/