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Receptors P1 and P2 as Targets for Drug Therapy in Humans最新文献

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Functions of Purinergic Receptors 嘌呤能受体的功能
Pub Date : 2019-12-24 DOI: 10.5772/intechopen.88251
E. Sarıkaya
Purinergic receptors, also known as purinoceptors, are a family of plasma membrane molecules found in many mammalian tissues. Purinergic receptors are transmembrane receptors consisting of two main categories. P1 receptors are stimulated by adenosine. Those that respond to extracellular nucleotides (ATP, ADP, UTP and UDP) are P2 receptors. The P2X receptors are ligand-gated ion channels. The P1 and P2Y receptors are bound to the G protein. Both of these metabotropic receptors are distinguished by taking into account their reactivity to specific activators. P1 and P2Y receptors are widely distributed in the brain, heart, kidneys and adipose tissue.
嘌呤能受体,也被称为嘌呤受体,是在许多哺乳动物组织中发现的一个质膜分子家族。嘌呤能受体是跨膜受体,主要分为两大类。P1受体受腺苷刺激。那些对细胞外核苷酸(ATP, ADP, UTP和UDP)有反应的是P2受体。P2X受体是配体门控离子通道。P1和P2Y受体与G蛋白结合。这两种代谢受体是通过考虑它们对特定激活剂的反应性来区分的。P1和P2Y受体广泛分布于大脑、心脏、肾脏和脂肪组织。
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引用次数: 0
Purinergic Signaling and Dental Orofacial Pain 嘌呤能信号与口腔面部疼痛
Pub Date : 2019-11-28 DOI: 10.5772/intechopen.87181
Xiuxin Liu
Pain is a common complaint of patients in the dental clinic. Patient with dental orofacial pain usually presents with hyperalgesia and allodynia. Its management has been a challenge, especially in the status of chronic pain or neuropathic pain. Purinergic signaling is dictated by ATP release, purinergic receptors activation, and sequential hydrolysis of ATP. Purinergic signaling participates in nociception processing in the sensory nerves by control of pain signal transduction, modulation, and sensitization. Since purinergic receptors are preferentially expressed in trigeminal nerves, purinergic singling may play a crucial role in the development of dental orofacial pain. In this chapter, we overview the expressions of purinergic receptors as well as the machinery for ATP release, ATP degradations, and adenosine generation in trigeminal nerves. Specifically, the roles of ATP signaling in dental orofacial pain generation and central sensitization via activation of P2 receptors and adenosine signaling in analgesia via activation of P1 receptors in trigeminal nerves are updated. We also discuss the affection of ecto-nucleotidases, the major enzymes responsible for extracellular ATP degradation and adenosine generation in trigeminal nerves that drive the shift from ATP-induced pain to adenosine-induced analgesia. This chapter provides advanced outlines for purinergic signaling in trigeminal nerves and unveils potential therapeutic targets for the management of dental orofacial pain.
疼痛是牙科诊所病人的常见主诉。口腔面部疼痛患者通常表现为痛觉过敏和异常性疼痛。其管理一直是一个挑战,特别是在慢性疼痛或神经性疼痛的状态。嘌呤能信号是由ATP释放、嘌呤能受体激活和ATP的顺序水解所决定的。嘌呤能信号通过控制疼痛信号的转导、调节和致敏参与感觉神经的痛觉加工。由于嘌呤能受体优先在三叉神经中表达,嘌呤能单化可能在口腔颌面部疼痛的发生中起关键作用。在本章中,我们概述了嘌呤能受体的表达以及三叉神经中ATP释放、ATP降解和腺苷生成的机制。具体来说,ATP信号通过激活P2受体在口腔面部疼痛产生和中枢致敏中的作用以及腺苷信号通过激活三叉神经P1受体在镇痛中的作用得到了更新。我们还讨论了外核苷酸酶的影响,外核苷酸酶是三叉神经中负责细胞外ATP降解和腺苷生成的主要酶,它推动了从ATP诱导的疼痛到腺苷诱导的镇痛的转变。本章提供了先进的概述嘌呤能信号在三叉神经和揭示潜在的治疗目标管理口腔面部疼痛。
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引用次数: 0
The Role of Purinergic Signaling in the Pathophysiology of Perinatal Hypoxic-Ischemic Encephalopathy 嘌呤能信号在围产期缺氧缺血性脑病病理生理中的作用
Pub Date : 2019-07-30 DOI: 10.5772/INTECHOPEN.86425
Tagore M. Morais-Lima, J. Vicentini, A. P. Alberto, Pedro Henrique Moreira de Freitas, C. Perret, Natiele Carla da Silva Ferreira, Deepaneeta Sarmah, B. Sinha, G. Das, P. Bhattacharya, Xin Wang, L. A. Alves, R. Rozental
Perinatal hypoxic-ischemic encephalopathy (HIE), known as birth asphyxia, remains a major contributor to poor neurodevelopmental outcomes including cerebral palsy and seizures. One striking feature of HIE injury is a delayed progression of neuronal degeneration that spreads over time from the most severely damaged areas outward into neighboring undamaged regions. There is increasing evidence that these lesions act as sites of origin for waves of spreading depression (SD), a wave of neuronal and glial depolarization, that progressively enlarge the brain lesions. While the pathophysiology of SD is still under debate, there is increasing evidence that purinergic receptors in conjunction with connexin and pannexin 1 channels are necessary for sustained propagation of the waves and neuroinflammation. This review intends to discuss the relative contribution of purinergic signaling and connexin and pannexin 1 channels to trigger and spread SD waves leading to the development of progressive brain lesions under conditions of perinatal HIE.
围产期缺氧缺血性脑病(HIE),称为出生窒息,仍然是神经发育不良的主要原因,包括脑瘫和癫痫发作。HIE损伤的一个显著特征是神经元退化的延迟进展,随着时间的推移,从最严重的受损区域向外扩散到邻近的未受损区域。越来越多的证据表明,这些病变是扩散性抑郁波(SD)的起源部位,SD是一种神经元和胶质去极化波,会逐渐扩大脑病变。虽然SD的病理生理学仍有争议,但越来越多的证据表明,嘌呤能受体与连接蛋白和泛连接蛋白1通道结合,对于波的持续传播和神经炎症是必要的。本文旨在探讨围产期HIE条件下嘌呤能信号和连接蛋白及泛连接蛋白1通道在SD波的触发和传播中所起的相对作用。
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引用次数: 0
A Brief View of Molecular Modeling Approaches to P2 Receptors P2受体分子模拟方法综述
Pub Date : 2019-07-30 DOI: 10.5772/INTECHOPEN.86862
A. P. Alberto, L. Santos, R. Ferreira, D. N. M. Ferreira, L. A. Alves
Purinergic receptors are a class of receptors distributed into two groups, P1 and P2. P1 receptors are activated by nucleosides, like adenosine, while nucleotides active P2 receptors. In turn, P2 receptors comprise two families, metabotropic P2Y and ionotropic P2X. P2Y receptors consist in eight members, namely, P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14, described in mammals, while P2X includes seven members, numbered P2X1 to P2X7. These receptors have been described as expressed in practically all cells studied to date. In this context, P2 receptors are suggested as participating in certain diseases. The general approach applied in the discovery of new drugs is expensive and lengthy. Alternatively, in the last 20 years, molecular modeling has emerged as an exciting tool for the design of new drugs, in less time and at low costs. These tools allow for in silico testing of thousands of molecules against a target protein, as well as toxicity, absorption, distribution, metabolism, and constant affinity predictions of a given interaction. Thus, molecular modeling algorithms emerge as an increasingly important tool for the design of drugs targeting purinergic receptors as therapeutic targets of many diseases, including cancer, pain, inflammation, cardiovascular, and endocrine conditions.
嘌呤能受体是一类分布在P1和P2两组的受体。P1受体被核苷激活,如腺苷,而核苷酸激活P2受体。反过来,P2受体包括两个家族,代谢性P2Y和离子性P2X。P2Y受体在哺乳动物中有8个成员,分别为P2Y1、P2Y2、P2Y4、P2Y6、P2Y11、P2Y12、P2Y13和P2Y14,而P2X包括7个成员,编号为P2X1至P2X7。到目前为止,这些受体在几乎所有的细胞中都有表达。在这种情况下,P2受体被认为参与了某些疾病。一般用于发现新药的方法既昂贵又耗时。另外,在过去的20年里,分子建模已经成为一种令人兴奋的新药物设计工具,在更短的时间和更低的成本。这些工具允许在计算机上测试针对目标蛋白的数千个分子,以及毒性、吸收、分布、代谢和给定相互作用的持续亲和力预测。因此,分子建模算法成为设计靶向嘌呤能受体的药物的一个越来越重要的工具,嘌呤能受体是许多疾病的治疗靶点,包括癌症、疼痛、炎症、心血管和内分泌疾病。
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引用次数: 1
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Receptors P1 and P2 as Targets for Drug Therapy in Humans
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