在小鼠实验性结肠炎期间,G蛋白结合受体18的激活
M Jurkiewicz1, G Stec1, W Machelak1
1Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
概括
这项研究研究了PSB-KK-1415,一种G蛋白结合受体18 (GPR18) 激动剂,用于治疗小鼠性结肠炎 (UC). 结果显示,GPR18激活可能有助于管理慢性结肠炎.
科学领域:
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 性结肠炎 (UC) 是一种慢性炎症性肠病 (IBD),患病率越来越高.
- 目前对UC的治疗方法无法实现完全缓解,因此需要新的治疗策略.
- G蛋白结合受体18 (GPR18) 是调节肠道炎症的潜在目标.
研究的目的:
- 评估PSB-KK-1415的治疗潜力,GPR18受体激动剂,在肠道炎症的小鼠模型中.
- 评估PSB-KK-1415对人类上皮细胞活性的影响.
- 为了研究GPR18在结肠炎不同阶段的表达.
主要方法:
- 使用MTT试验评估了PSB-KK-1415对CCD 841 CON细胞活性的影响.
- 德克斯硫酸 (DSS) 用于诱导小鼠的急性和慢性结肠炎.
- 使用实时RT-PCR量化GPR18mRNA表达;用宏观和显微镜评估抗炎作用.
主要成果:
- PSB-KK-1415没有影响上皮细胞活力.
- 在早期/中度结肠炎中,GPR18 mRNA的表达上调,在严重结肠炎/恢复中下调.
- 在DSS诱导的大肠炎模型中,PSB-KK-1415治疗减少了结肠炎症,改善了肠壁厚度,并降低了MPO活性.
结论:
- GPR18受体的激活显示出治疗肠道炎症的前景.
- 在UC的小鼠模型中,PSB-KK-1415显示出抗炎性质.
- 准GPR18可能是治疗慢性结肠炎的可行策略.
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相关概念视频
G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
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