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嘌呤能受体调节剂:一种用于疾病管理的新兴药理学工具。

Purinergic receptors modulators: An emerging pharmacological tool for disease management.

作者信息

Mahmood Abid, Iqbal Jamshed

机构信息

Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad, Pakistan.

出版信息

Med Res Rev. 2022 Jul;42(4):1661-1703. doi: 10.1002/med.21888. Epub 2022 May 13.

Abstract

Purinergic signaling is mediated through extracellular nucleotides (adenosine 5'-triphosphate, uridine-5'-triphosphate, adenosine diphosphate, uridine-5'-diphosphate, and adenosine) that serve as signaling molecules. In the early 1990s, purines and pyrimidine receptors were cloned and characterized drawing the attention of scientists toward this aspect of cellular signaling. This signaling pathway is comprised of four subtypes of adenosine receptors (P1), eight subtypes of G-coupled protein receptors (P2YRs), and seven subtypes of ligand-gated ionotropic receptors (P2XRs). In current studies, the pathophysiology and therapeutic potentials of these receptors have been focused on. Various ligands, modulating the functions of purinergic receptors, are in current clinical practices for the treatment of various neurodegenerative disorders and cardiovascular diseases. Moreover, several purinergic receptors ligands are in advanced phases of clinical trials as a remedy for depression, epilepsy, autism, osteoporosis, atherosclerosis, myocardial infarction, diabetes, irritable bowel syndrome, and cancers. In the present study, agonists and antagonists of purinergic receptors have been summarized that may serve as pharmacological tools for drug design and development.

摘要

嘌呤能信号传导是通过作为信号分子的细胞外核苷酸(腺苷5'-三磷酸、尿苷-5'-三磷酸、腺苷二磷酸、尿苷-5'-二磷酸和腺苷)介导的。在20世纪90年代初,嘌呤和嘧啶受体被克隆并进行了表征,引起了科学家对细胞信号传导这一方面的关注。该信号通路由四种腺苷受体亚型(P1)、八种G蛋白偶联受体亚型(P2YRs)和七种配体门控离子型受体亚型(P2XRs)组成。在当前的研究中,这些受体的病理生理学和治疗潜力受到了关注。各种调节嘌呤能受体功能的配体目前在治疗各种神经退行性疾病和心血管疾病的临床实践中使用。此外,几种嘌呤能受体配体正处于临床试验的后期阶段,用于治疗抑郁症、癫痫、自闭症、骨质疏松症、动脉粥样硬化、心肌梗死、糖尿病、肠易激综合征和癌症。在本研究中,总结了嘌呤能受体的激动剂和拮抗剂,它们可作为药物设计和开发的药理学工具。

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