Purinergic regulation of pulmonary vascular tone.

IF 3 4区 医学 Q2 NEUROSCIENCES Purinergic Signalling Pub Date : 2024-12-01 Epub Date: 2024-05-07 DOI:10.1007/s11302-024-10010-5
Marco Alveal, Andrea Méndez, Aline García, Mauricio Henríquez
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Abstract

Purinergic signaling is a crucial determinant in the regulation of pulmonary vascular physiology and presents a promising avenue for addressing lung diseases. This intricate signaling system encompasses two primary receptor classes: P1 and P2 receptors. P1 receptors selectively bind adenosine, while P2 receptors exhibit an affinity for ATP, ADP, UTP, and UDP. Functionally, P1 receptors are associated with vasodilation, while P2 receptors mediate vasoconstriction, particularly in basally relaxed vessels, through modulation of intracellular Ca2+ levels. The P2X subtype receptors facilitate extracellular Ca2+ influx, while the P2Y subtype receptors are linked to endoplasmic reticulum Ca2+ release. Notably, the primary receptor responsible for ATP-induced vasoconstriction is P2X1, with α,β-meATP and UDP being identified as potent vasoconstrictor agonists. Interestingly, ATP has been shown to induce endothelium-dependent vasodilation in pre-constricted vessels, associated with nitric oxide (NO) release. In the context of P1 receptors, adenosine stimulation of pulmonary vessels has been unequivocally demonstrated to induce vasodilation, with a clear dependency on the A2B receptor, as evidenced in studies involving guinea pigs and rats. Importantly, evidence strongly suggests that this vasodilation occurs independently of endothelium-mediated mechanisms. Furthermore, studies have revealed variations in the expression of purinergic receptors across different vessel sizes, with reports indicating notably higher expression of P2Y1, P2Y2, and P2Y4 receptors in small pulmonary arteries. While the existing evidence in this area is still emerging, it underscores the urgent need for a comprehensive examination of the specific characteristics of purinergic signaling in the regulation of pulmonary vascular tone, particularly focusing on the disparities observed across different intrapulmonary vessel sizes. Consequently, this review aims to meticulously explore the current evidence regarding the role of purinergic signaling in pulmonary vascular tone regulation, with a specific emphasis on the variations observed in intrapulmonary vessel sizes. This endeavor is critical, as purinergic signaling holds substantial promise in the modulation of vascular tone and in the proactive prevention and treatment of pulmonary vascular diseases.

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嘌呤能调节肺血管张力。
嘌呤能信号是调控肺血管生理机能的重要决定因素,也是治疗肺部疾病的有效途径。这一复杂的信号系统包括两个主要的受体类别:P1 和 P2 受体。P1 受体选择性地结合腺苷,而 P2 受体则对 ATP、ADP、UTP 和 UDP 具有亲和力。在功能上,P1 受体与血管扩张有关,而 P2 受体则通过调节细胞内 Ca2+ 水平介导血管收缩,尤其是在基础松弛的血管中。P2X 亚型受体促进细胞外 Ca2+ 的流入,而 P2Y 亚型受体则与内质网 Ca2+ 的释放有关。值得注意的是,P2X1 是 ATP 诱导血管收缩的主要受体,α,β-meATP 和 UDP 被认为是强效的血管收缩激动剂。有趣的是,在收缩前的血管中,ATP 可诱导内皮依赖性血管扩张,这与一氧化氮(NO)的释放有关。在 P1 受体方面,腺苷对肺血管的刺激已被明确证实可诱导血管舒张,并明显依赖于 A2B 受体,这在涉及豚鼠和大鼠的研究中得到了证明。重要的是,有证据有力地表明,这种血管扩张的发生与内皮介导的机制无关。此外,研究还发现不同大小的血管中嘌呤能受体的表达存在差异,有报告显示肺小动脉中 P2Y1、P2Y2 和 P2Y4 受体的表达明显较高。虽然这一领域的现有证据仍在不断涌现,但它强调了对嘌呤能信号调节肺血管张力的具体特征进行全面研究的迫切需要,尤其是重点研究在不同大小的肺内血管中观察到的差异。因此,本综述旨在仔细探讨有关嘌呤能信号在肺血管张力调节中的作用的现有证据,并特别强调在肺内血管大小中观察到的差异。这项工作至关重要,因为嘌呤能信号在调节血管张力以及积极预防和治疗肺血管疾病方面大有可为。
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来源期刊
Purinergic Signalling
Purinergic Signalling 医学-神经科学
CiteScore
6.60
自引率
17.10%
发文量
75
审稿时长
6-12 weeks
期刊介绍: Nucleotides and nucleosides are primitive biological molecules that were utilized early in evolution both as intracellular energy sources and as extracellular signalling molecules. ATP was first identified as a neurotransmitter and later as a co-transmitter with all the established neurotransmitters in both peripheral and central nervous systems. Four subtypes of P1 (adenosine) receptors, 7 subtypes of P2X ion channel receptors and 8 subtypes of P2Y G protein-coupled receptors have currently been identified. Since P2 receptors were first cloned in the early 1990’s, there is clear evidence for the widespread distribution of both P1 and P2 receptor subtypes in neuronal and non-neuronal cells, including glial, immune, bone, muscle, endothelial, epithelial and endocrine cells.
期刊最新文献
Correction to: Preparation and preliminary evaluation of a tritium-labeled allosteric P2X4 receptor antagonist. Machine learning-aided search for ligands of P2Y6 and other P2Y receptors. Purinergic regulation of pulmonary vascular tone. Role of ecto-5'-nucleotidase in bladder function activity and smooth muscle contractility. Unexpected role of microglia and P2Y12 in the induction of and emergence from anesthesia.
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