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International Journal of Molecular... Nov 2021ATP is stored in millimolar concentrations within the intracellular medium but may be released to extracellular sites either through the damaged plasma membrane or by...
ATP is stored in millimolar concentrations within the intracellular medium but may be released to extracellular sites either through the damaged plasma membrane or by means of various transporters [...].
Topics: Animals; Humans; Neuroinflammatory Diseases; Purines; Receptors, Purinergic; Signal Transduction
PubMed: 34884700
DOI: 10.3390/ijms222312895 -
Sub-cellular Biochemistry 2011The current treatments offered to patients with chronic respiratory diseases are being re-evaluated based on the loss of potency during long-term treatments or because... (Review)
Review
The current treatments offered to patients with chronic respiratory diseases are being re-evaluated based on the loss of potency during long-term treatments or because they only provide significant clinical benefits to a subset of the patient population. For instance, glucocorticoids are considered the most effective anti-inflammatory therapies for chronic inflammatory and immune diseases, such as asthma. But they are relatively ineffective in asthmatic smokers, and patients with chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF). As such, the pharmaceutical industry is exploring new therapeutic approaches to address all major respiratory diseases. The previous chapters demonstrated the widespread influence of purinergic signaling on all pulmonary functions and defense mechanisms. In Chap. 8, we described animal studies which highlighted the critical role of aberrant purinergic activities in the development and maintenance of chronic airway diseases. This last chapter covers all clinical and pharmaceutical applications currently developed based on purinergic receptor agonists and antagonists. We use the information acquired in the previous chapters on purinergic signaling and lung functions to scrutinize the preclinical and clinical data, and to realign the efforts of the pharmaceutical industry.
Topics: Animals; Biomarkers; Epithelial Cells; Humans; Lung Diseases; Molecular Targeted Therapy; Predictive Value of Tests; Purinergic Agonists; Purinergic Antagonists; Purines; Receptors, Purinergic; Respiratory Mucosa; Signal Transduction
PubMed: 21560050
DOI: 10.1007/978-94-007-1217-1_9 -
International Journal of Molecular... May 2023Since its inception by the late Geoffrey Burnstock in the early 1970s [...].
Since its inception by the late Geoffrey Burnstock in the early 1970s [...].
Topics: Receptors, Purinergic; Signal Transduction; Biological Phenomena; Adenosine Triphosphate
PubMed: 37298149
DOI: 10.3390/ijms24119196 -
Journal of Leukocyte Biology Nov 2022Since their discovery in the 1970s, purinergic receptors have been shown to play key roles in a wide variety of biologic systems and cell types. In the immune system,... (Review)
Review
Since their discovery in the 1970s, purinergic receptors have been shown to play key roles in a wide variety of biologic systems and cell types. In the immune system, purinergic receptors participate in innate immunity and in the modulation of the adaptive immune response. In particular, P2 receptors, which respond to extracellular nucleotides, are widely expressed on leukocytes, causing the release of cytokines and chemokines and the formation of inflammatory mediators, and inducing phagocytosis, degranulation, and cell death. The activity of these receptors is regulated by ectonucleotidases-expressed in these same cell types-which regulate the availability of nucleotides in the extracellular environment. In this article, we review the characteristics of the main purinergic receptor subtypes present in the immune system, focusing on the P2 family. In addition, we describe the physiologic roles of the P2 receptors already identified in leukocytes and how they can positively or negatively modulate the development of infectious diseases, inflammation, and pain.
Topics: Receptors, Purinergic; Nucleotides; Inflammation Mediators; Leukocytes; Cytokines; Biological Products; Adenosine Triphosphate
PubMed: 35837975
DOI: 10.1002/JLB.2RU0421-226RR -
International Journal of Molecular... Jan 2021Increased vascular permeability is a hallmark of several cardiovascular anomalies, including ischaemia/reperfusion injury and inflammation. During both... (Review)
Review
Increased vascular permeability is a hallmark of several cardiovascular anomalies, including ischaemia/reperfusion injury and inflammation. During both ischaemia/reperfusion and inflammation, massive amounts of various nucleotides, particularly adenosine 5'-triphosphate (ATP) and adenosine, are released that can induce a plethora of signalling pathways via activation of several purinergic receptors and may affect endothelial barrier properties. The nature of the effects on endothelial barrier function may depend on the prevalence and type of purinergic receptors activated in a particular tissue. In this review, we discuss the influence of the activation of various purinergic receptors and downstream signalling pathways on vascular permeability during pathological conditions.
Topics: Adenosine; Animals; Biomarkers; Blood-Air Barrier; Blood-Brain Barrier; Capillary Permeability; Endothelium; Humans; Purines; Receptors, Purinergic; Receptors, Purinergic P2; Signal Transduction
PubMed: 33530557
DOI: 10.3390/ijms22031207 -
Journal of the American Heart... Sep 2020Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by increased pulmonary arterial pressure and pulmonary vascular resistance, which... (Review)
Review
Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by increased pulmonary arterial pressure and pulmonary vascular resistance, which result in an increase in afterload imposed onto the right ventricle, leading to right heart failure. Current therapies are incapable of reversing the disease progression. Thus, the identification of novel and potential therapeutic targets is urgently needed. An alteration of nucleotide- and nucleoside-activated purinergic signaling has been proposed as a potential contributor in the pathogenesis of PAH. Adenosine-mediated purinergic 1 receptor activation, particularly AR activation, reduces pulmonary vascular resistance and attenuates pulmonary vascular remodeling and right ventricle hypertrophy, thereby exerting a protective effect. Conversely, AR activation induces pulmonary vascular remodeling, and is therefore deleterious. ATP-mediated P2XR activation and ADP-mediated activation of P2YR and P2YR play a role in pulmonary vascular tone, vascular remodeling, and inflammation in PAH. Recent studies have revealed a role of ectonucleotidase nucleoside triphosphate diphosphohydrolase, that degrades ATP/ADP, in regulation of pulmonary vascular remodeling. Interestingly, existing evidence that adenosine activates erythrocyte AR signaling, counteracting hypoxia-induced pulmonary injury, and that ATP release is impaired in erythrocyte in PAH implies erythrocyte dysfunction as an important trigger to affect purinergic signaling for pathogenesis of PAH. The present review focuses on current knowledge on alteration of nucleot(s)ide-mediated purinergic signaling as a potential disease mechanism underlying the development of PAH.
Topics: Animals; Humans; Pulmonary Arterial Hypertension; Purinergic Agents; Receptors, Purinergic
PubMed: 32867554
DOI: 10.1161/JAHA.120.017404 -
Cells Jul 2020Cancer is a complex expression of an altered state of cellular differentiation associated with severe clinical repercussions. The effort to characterize this... (Review)
Review
Cancer is a complex expression of an altered state of cellular differentiation associated with severe clinical repercussions. The effort to characterize this pathological entity to understand its underlying mechanisms and visualize potential therapeutic strategies has been constant. In this context, some cellular (enhanced duplication, immunological evasion), metabolic (aerobic glycolysis, failure in DNA repair mechanisms) and physiological (circadian disruption) parameters have been considered as cancer hallmarks. The list of these hallmarks has been growing in recent years, since it has been demonstrated that various physiological systems misfunction in well-characterized ways upon the onset and establishment of the carcinogenic process. This is the case with the purinergic system, a signaling pathway formed by nucleotides/nucleosides (mainly adenosine triphosphate (ATP), adenosine (ADO) and uridine triphosphate (UTP)) with their corresponding membrane receptors and defined transduction mechanisms. The dynamic equilibrium between ATP and ADO, which is accomplished by the presence and regulation of a set of ectonucleotidases, defines the pro-carcinogenic or anti-cancerous final outline in tumors and cancer cell lines. So far, the purinergic system has been recognized as a potential therapeutic target in cancerous and tumoral ailments.
Topics: Adenosine Triphosphate; Animals; Humans; Neoplasms; Receptors, Purinergic; Signal Transduction; Tumor Microenvironment
PubMed: 32635260
DOI: 10.3390/cells9071612 -
The Journal of Biological Chemistry Apr 1992With the recent purification and cloning of the A1AR and the cloning of the A2AR in association with the development of selective radioligands, we are now poised to... (Review)
Review
With the recent purification and cloning of the A1AR and the cloning of the A2AR in association with the development of selective radioligands, we are now poised to begin to understand at the most fundamental level the structure, function, and regulation of adenosine receptors. Although adenosine's physiological effects have been appreciated for more than 60 years, we are only now ready to address questions at the biochemical and molecular biological levels. We are likely to begin to see evidence for a whole group of adenosine receptors undetected by previous technology. One era of adenosine receptor research has just ended, and we now enter the new with anxious anticipation.
Topics: Amino Acid Sequence; Animals; GTP-Binding Proteins; Molecular Sequence Data; Receptors, Purinergic; Signal Transduction
PubMed: 1551861
DOI: No ID Found -
Neuropharmacology Oct 2023The purinergic system includes P1 and P2 receptors, which are activated by ATP and its metabolites. They are expressed in adult neuronal and glial cells and are crucial... (Review)
Review
The purinergic system includes P1 and P2 receptors, which are activated by ATP and its metabolites. They are expressed in adult neuronal and glial cells and are crucial in brain function, including neuromodulation and neuronal signaling. As P1 and P2 receptors are expressed throughout embryogenesis and development, purinergic signaling also has an important role in the development of the peripheral and central nervous system. In this review, we present the expression pattern and activity of purinergic receptors and of their signaling pathways during embryonic and postnatal development of the nervous system. In particular, we review the involvement of the purinergic signaling in all the crucial steps of brain development i.e. in neural stem cell proliferation, neuronal differentiation and migration as well as in astrogliogenesis and oligodendrogenesis. Then, we review data showing a crucial role of the ATP and adenosine signaling pathways in the formation of the peripheral neuromuscular junction and of central GABAergic and glutamatergic synapses. Finally, we examine the consequences of deregulation of the purinergic system during development and discuss the therapeutic potential of targeting it at adult stage in diseases with reactivation of the ATP and adenosine pathway. This article is part of the Special Issue on "Purinergic Signaling: 50 years".
Topics: Neurons; Receptors, Purinergic; Adenosine; Adenosine Triphosphate; Brain; Cell Proliferation
PubMed: 37348675
DOI: 10.1016/j.neuropharm.2023.109640 -
Kidney International Feb 2017Nucleotides are key subunits for nucleic acids and provide energy for intracellular metabolism. They can also be released from cells to act physiologically as... (Review)
Review
Nucleotides are key subunits for nucleic acids and provide energy for intracellular metabolism. They can also be released from cells to act physiologically as extracellular messengers or pathologically as danger signals. Extracellular nucleotides stimulate membrane receptors in the P2 and P1 family. P2X are ATP-activated cation channels; P2Y and P1 are G-protein coupled receptors activated by ATP, ADP, UTP, and UDP in the case of P2 or adenosine for P1. Renal P2 receptors influence both vascular contractility and tubular function. Renal cells also express ectonucleotidases that rapidly hydrolyze extracellular nucleotides. These enzymes integrate this multireceptor purinergic-signaling complex by determining the nucleotide milieu to titrate receptor activation. Purinergic signaling also regulates immune cell function by modulating the synthesis and release of various cytokines such as IL1-β and IL-18 as part of inflammasome activation. Abnormal or excessive stimulation of this intricate paracrine system can be pro- or anti-inflammatory, and is also linked to necrosis and apoptosis. Kidney tissue injury causes a localized increase in ATP concentration, and sustained activation of P2 receptors can lead to renal glomerular, tubular, and vascular cell damage. Purinergic receptors also regulate the activity and proliferation of fibroblasts, promoting both inflammation and fibrosis in chronic disease. In this short review we summarize some of the recent findings related to purinergic signaling in the kidney. We focus predominantly on the P2X7 receptor, discussing why antagonists have so far disappointed in clinical trials and how advances in our understanding of purinergic signaling might help to reposition these compounds as potential treatments for renal disease.
Topics: Adenosine; Animals; Humans; Kidney; Kidney Diseases; Ligands; Purine Nucleotides; Purinergic P2X Receptor Antagonists; Receptors, Purinergic P1; Receptors, Purinergic P2; Receptors, Purinergic P2X7; Signal Transduction
PubMed: 27780585
DOI: 10.1016/j.kint.2016.08.029