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Purinergic Signalling Dec 2014This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to... (Review)
Review
This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells.
Topics: Animals; Humans; Immune System; Purines; Receptors, Purinergic; Signal Transduction
PubMed: 25352330
DOI: 10.1007/s11302-014-9427-2 -
Frontiers in Immunology 2020Eosinophils are major effector cells against parasites, fungi, bacteria, and viruses. However, these cells also take part in local and systemic inflammation, which are... (Review)
Review
Eosinophils are major effector cells against parasites, fungi, bacteria, and viruses. However, these cells also take part in local and systemic inflammation, which are central to eczema, atopy, rhinitis, asthma, and autoimmune diseases. A role for eosinophils has been also shown in vascular thrombotic disorders and in cancer. Many, if not all, above-mentioned conditions involve the release of intracellular nucleotides (ATP, ADP, UTP, etc.) and nucleosides (adenosine) in the extracellular environment. Simultaneously, eosinophils further release ATP, which in autocrine and paracrine manners, stimulates P2 receptors. Purinergic signaling in eosinophils mediates a variety of responses including CD11b induction, ROI production, release of granule contents and enzymes, as well as cytokines. Exposure to extracellular ATP also modulates the expression of endothelial adhesion molecules, thereby favoring eosinophil extravasation and accumulation. In addition, eosinophils express the immunosuppressive adenosine P1 receptors, which regulate degranulation and migration. However, pro-inflammatory responses induced by extracellular ATP predominate. Due to their important role in innate immunity and tissue damage, pharmacological targeting of nucleotide- and nucleoside-mediated signaling in eosinophils could represent a novel approach to alleviate eosinophilic acute and chronic inflammatory diseases. These innovative approaches might also have salutary effects, particularly in host defense against parasites and in cancer.
Topics: Animals; Eosinophils; Humans; Inflammation; Receptors, Purinergic; Signal Transduction
PubMed: 32733449
DOI: 10.3389/fimmu.2020.01339 -
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 -
Purinergic Signalling Jun 2018Obesity is a growing worldwide health problem, with an alarming increasing prevalence in developed countries, caused by a dysregulation of energy balance. Currently, no... (Review)
Review
Obesity is a growing worldwide health problem, with an alarming increasing prevalence in developed countries, caused by a dysregulation of energy balance. Currently, no wholly successful pharmacological treatments are available for obesity and related adverse consequences. In recent years, hints obtained from several experimental animal models support the notion that purinergic signalling, acting through ATP-gated ion channels (P2X), G protein-coupled receptors (P2Y) and adenosine receptors (P1), is involved in obesity, both at peripheral and central levels. This review has drawn together, for the first time, the evidence for a promising, much needed novel therapeutic purinergic signalling approach for the treatment of obesity with a 'proof of concept' that hopefully could lead to further investigations and clinical trials for the management of obesity.
Topics: Animals; Humans; Obesity; Receptors, Purinergic; Signal Transduction
PubMed: 29619754
DOI: 10.1007/s11302-018-9605-8 -
Handbook of Experimental Pharmacology 2022This review summarizes our understanding of ATP signaling in taste and describes new directions for research. ATP meets all requisite criteria to be considered a... (Review)
Review
This review summarizes our understanding of ATP signaling in taste and describes new directions for research. ATP meets all requisite criteria to be considered a neurotransmitter: (1) presence in taste cells, as in all cells; (2) release upon appropriate taste stimulation; (3) binding to cognate purinergic receptors P2X2 and P2X3 on gustatory afferent neurons, and (4) after release, enzymatic degradation to adenosine and other nucleotides by the ectonucleotidase, NTPDase2, expressed on the Type I, glial-like cells in the taste bud. Importantly, double knockout of P2X2 and P2X3 or pharmacological inhibition of P2X3 abolishes transmission of all taste qualities. In Type II taste cells (those that respond to sweet, bitter, or umami stimuli), ATP is released non-vesicularly by a large conductance ion channel composed of CALHM1 and CALHM3, which form a so-called channel synapse at areas of contact with afferent taste nerve fibers. Although ATP release has been detected only from Type II cells, it is also required for the transmission of salty and sour stimuli, which are mediated primarily by the Type III taste cells. The source of the ATP required for Type III cell signaling to afferent fibers is still unclear and is a focus for future experiments. The ionotropic purinergic receptor, P2X3, is widely expressed on many sensory afferents and has been a therapeutic target for treating chronic cough and pain. However, its requirement for taste signaling has complicated efforts at treatment since patients given P2X3 antagonists report substantial disturbances of taste and become non-compliant.
Topics: Adenosine Triphosphate; Humans; Receptors, Purinergic; Signal Transduction; Taste; Taste Buds
PubMed: 34435233
DOI: 10.1007/164_2021_518 -
Glia Aug 2021To facilitate analyses of purinergic signaling in peripheral nerve glia, we review recent literature and catalog purinergic receptor mRNA expression in cultured mouse... (Review)
Review
To facilitate analyses of purinergic signaling in peripheral nerve glia, we review recent literature and catalog purinergic receptor mRNA expression in cultured mouse Schwann cells (SCs). Purinergic signaling can decrease developmental SC proliferation, and promote SC differentiation. The purinergic receptors P2RY2 and P2RX7 are implicated in nerve development and in the ratio of Remak SCs to myelinating SCs in differentiated peripheral nerve. P2RY2, P2RX7, and other receptors are also implicated in peripheral neuropathies and SC tumors. In SC tumors lacking the tumor suppressor NF1, the SC pathway that suppresses SC growth through P2RY2-driven β-arrestin-mediated AKT signaling is aberrant. SC-released purinergic agonists acting through SC and/or neuronal purinergic receptors activate pain responses. In all these settings, purinergic receptor activation can result in calcium-independent and calcium-dependent release of SC ATP and UDP, growth factors, and cytokines that may contribute to disease and nerve repair. Thus, current research suggests that purinergic agonists and/or antagonists might have the potential to modulate peripheral glia function in development and in disease.
Topics: Animals; Mice; Neuroglia; Peripheral Nervous System Diseases; Receptors, Purinergic; Schwann Cells; Signal Transduction
PubMed: 33507559
DOI: 10.1002/glia.23969 -
Purinergic Signalling Sep 2015Extracellular purines and pyrimidines play major roles during embryogenesis, organogenesis, postnatal development and ageing in vertebrates, including humans.... (Review)
Review
Extracellular purines and pyrimidines play major roles during embryogenesis, organogenesis, postnatal development and ageing in vertebrates, including humans. Pluripotent stem cells can differentiate into three primary germ layers of the embryo but may also be involved in plasticity and repair of the adult brain. These cells express the molecular components necessary for purinergic signalling, and their developmental fates can be manipulated via this signalling pathway. Functional P1, P2Y and P2X receptor subtypes and ectonucleotidases are involved in the development of different organ systems, including heart, blood vessels, skeletal muscle, urinary bladder, central and peripheral neurons, retina, inner ear, gut, lung and vas deferens. The importance of purinergic signalling in the ageing process is suggested by changes in expression of A1 and A2 receptors in old rat brains and reduction of P2X receptor expression in ageing mouse brain. By contrast, in the periphery, increases in expression of P2X3 and P2X4 receptors are seen in bladder and pancreas.
Topics: Adult; Aging; Animals; Embryonic Development; Female; Humans; Pregnancy; Purines; Receptors, Purinergic; Signal Transduction; Stem Cells
PubMed: 25989750
DOI: 10.1007/s11302-015-9452-9 -
Purinergic Signalling Sep 2021Cancer comprises a collection of diseases that occur in almost any tissue and it is characterized by an abnormal and uncontrolled cell growth that results in tumor... (Review)
Review
Cancer comprises a collection of diseases that occur in almost any tissue and it is characterized by an abnormal and uncontrolled cell growth that results in tumor formation and propagation to other tissues, causing tissue and organ malfunction and death. Despite the undeniable improvement in cancer diagnostics and therapy, there is an urgent need for new therapeutic and preventive strategies with improved efficacy and fewer side effects. In this context, purinergic signaling emerges as an interesting candidate as a cancer biomarker or therapeutic target. There is abundant evidence that tumor cells have significant changes in the expression of purinergic receptors, which comprise the G-protein coupled P2Y and AdoR families of receptors and the ligand-gated ion channel P2X receptors. Tumor cells also exhibit changes in the expression of nucleotidases and other enzymes involved in nucleotide metabolism, and the concentrations of extracellular nucleotides are significantly higher than those observed in normal cells. In this review, we will focus on the potential role of purinergic signaling in the ten most lethal cancers (lung, breast, colorectal, liver, stomach, prostate, cervical, esophagus, pancreas, and ovary), which together are responsible for more than 5 million annual deaths.
Topics: Adenosine Triphosphate; Animals; Autocrine Communication; Humans; Neoplasms; Paracrine Communication; Receptors, Purinergic; Signal Transduction
PubMed: 33982134
DOI: 10.1007/s11302-021-09785-8 -
Purinergic Signalling Mar 2014There is widespread involvement of purinergic signalling in endocrine biology. Pituitary cells express P1, P2X and P2Y receptor subtypes to mediate hormone release.... (Review)
Review
There is widespread involvement of purinergic signalling in endocrine biology. Pituitary cells express P1, P2X and P2Y receptor subtypes to mediate hormone release. Adenosine 5'-triphosphate (ATP) regulates insulin release in the pancreas and is involved in the secretion of thyroid hormones. ATP plays a major role in the synthesis, storage and release of catecholamines from the adrenal gland. In the ovary purinoceptors mediate gonadotrophin-induced progesterone secretion, while in the testes, both Sertoli and Leydig cells express purinoceptors that mediate secretion of oestradiol and testosterone, respectively. ATP released as a cotransmitter with noradrenaline is involved in activities of the pineal gland and in the neuroendocrine control of the thymus. In the hypothalamus, ATP and adenosine stimulate or modulate the release of luteinising hormone-releasing hormone, as well as arginine-vasopressin and oxytocin. Functionally active P2X and P2Y receptors have been identified on human placental syncytiotrophoblast cells and on neuroendocrine cells in the lung, skin, prostate and intestine. Adipocytes have been recognised recently to have endocrine function involving purinoceptors.
Topics: Adenosine Triphosphate; Adipocytes; Adrenal Glands; Animals; Arginine Vasopressin; Endocrine Glands; Humans; Oxytocin; Receptors, Purinergic; Signal Transduction
PubMed: 24265070
DOI: 10.1007/s11302-013-9396-x -
Acta Physiologica (Oxford, England) Jun 2013
Topics: Animals; Humans; Purines; Receptors, Purinergic; Signal Transduction
PubMed: 23510384
DOI: 10.1111/apha.12098