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Brain Research Bulletin Sep 2019Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, characterized by the presence of focal lesions in white and grey... (Review)
Review
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, characterized by the presence of focal lesions in white and grey matter with peripheral immune cells infiltration. Purinergic receptors control immune cell function as well as neuronal and oligodendroglial survival, and the activation of astrocytes and microglia, the endogenous brain immune cells. In particular, ionotropic purinergic receptors P2X4 and P2X7 and metabotropic receptor P2Y12 are differently expressed along the disease and their activation or blockage modifies the course of texperimental autoimmune encephalomyelitis (EAE), the dominant animal model of MS. In this review, we will summarize emerging evidence of the role of these three receptor types as potential MS biomarkers and therapeutic targets.
Topics: Animals; Astrocytes; Brain; Central Nervous System; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Humans; Microglia; Multiple Sclerosis; Oligodendroglia; Receptors, Purinergic; Receptors, Purinergic P2X; Receptors, Purinergic P2Y; Signal Transduction
PubMed: 30500565
DOI: 10.1016/j.brainresbull.2018.11.018 -
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 -
Advances in Pharmacology (San Diego,... 2016There is a brief introductory summary of purinergic signaling involving ATP storage, release, and ectoenzymatic breakdown, and the current classification of receptor... (Review)
Review
There is a brief introductory summary of purinergic signaling involving ATP storage, release, and ectoenzymatic breakdown, and the current classification of receptor subtypes for purines and pyrimidines. The review then describes purinergic mechanosensory transduction involved in visceral, cutaneous, and musculoskeletal nociception and on the roles played by receptor subtypes in neuropathic and inflammatory pain. Multiple purinoceptor subtypes are involved in pain pathways both as an initiator and modulator. Activation of homomeric P2X3 receptors contributes to acute nociception and activation of heteromeric P2X2/3 receptors appears to modulate longer-lasting nociceptive sensitivity associated with nerve injury or chronic inflammation. In neuropathic pain activation of P2X4, P2X7, and P2Y12 receptors on microglia may serve to maintain nociceptive sensitivity through complex neural-glial cell interactions and antagonists to these receptors reduce neuropathic pain. Potential therapeutic approaches involving purinergic mechanisms will be discussed.
Topics: Analgesics; Animals; Humans; Mechanotransduction, Cellular; Migraine Disorders; Pain; Purinergic Antagonists; Receptors, Purinergic
PubMed: 26920010
DOI: 10.1016/bs.apha.2015.09.001 -
Molecular Psychiatry Jan 2018Psychiatric disorders are debilitating diseases, affecting >80 million people worldwide. There are no causal cures for psychiatric disorders and available therapies only... (Review)
Review
Psychiatric disorders are debilitating diseases, affecting >80 million people worldwide. There are no causal cures for psychiatric disorders and available therapies only treat the symptoms. The etiology of psychiatric disorders is unknown, although it has been speculated to be a combination of environmental, stress and genetic factors. One of the neurotransmitter systems implicated in the biology of psychiatric disorders is the purinergic system. In this review, we performed a comprehensive search of the literature about the role and function of the purinergic system in the development and predisposition to psychiatric disorders, with a focus on depression, schizophrenia, bipolar disorder, autism, anxiety and attention deficit/hyperactivity disorder. We also describe how therapeutics used for psychiatric disorders act on the purinergic system.
Topics: Animals; Causality; Humans; Mental Disorders; Purines; Receptors, Purinergic
PubMed: 28948971
DOI: 10.1038/mp.2017.188 -
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 -
Pharmacology, Biochemistry, and Behavior Nov 2019This review summarizes and evaluates the relationship between neuropathic pain and P2Y receptors from inception to 2019. Purinergic receptors have been well studied in... (Review)
Review
This review summarizes and evaluates the relationship between neuropathic pain and P2Y receptors from inception to 2019. Purinergic receptors have been well studied in recent years using various molecular biological methods. The main research objective of this review is to determine the association of P2Y1, P2Y2, P2Y6, P2Y12 and P2Y13 receptors with neuropathic pain. This review includes the most comprehensive subtypes of P2Y that related to neuropathic pain and the current therapeutic method of neuropathic pain. G protein-coupled P2Y receptors are located on neurons, astrocytes, oligodendrocytes and microglial cells and regulate neurotransmission. Nerve injury is the prime reason for abnormal regulation of P2Y receptor mRNA expression, subsequently, inducing neuropathic pain. Neuropathic pain is a type of chronic pain that is divided into peripheral, central and mixed. Numerous studies demonstrated a positive correlation between the expression level of P2Y receptors and neuropathic pain generation. Also, several reports showed that P2Y short hairpin RNA (shRNA) and P2Y antagonist can be used as an analgesic to relieve neuropathic pain via decreasing P2Y receptor expression level and neural cell activation. However, the transformation process from basic experiments to clinical applications is a long process. Current deficiencies and future research directions are discussed at the end of this review.
Topics: Animals; Humans; Neuralgia; Receptors, Purinergic P2; Signal Transduction
PubMed: 31494119
DOI: 10.1016/j.pbb.2019.172788 -
International Journal of Molecular... Nov 2020Endometriosis is an estrogen-dependent gynecological disease, with an associated chronic inflammatory component, characterized by the presence of endometrial tissue... (Review)
Review
Endometriosis is an estrogen-dependent gynecological disease, with an associated chronic inflammatory component, characterized by the presence of endometrial tissue outside the uterine cavity. Its predominant symptom is pain, a condition notably altering the quality of life of women with the disease. This review is intended to exhaustively gather current knowledge on purinergic signaling in endometriosis-associated pain. Altered extracellular ATP hydrolysis, due to changes in ectonucleotidase activity, has been reported in endometriosis; the resulting accumulation of ATP in the endometriotic microenvironment points to sustained activation of nucleotide receptors (P2 receptors) capable of generating a persistent pain message. P2X3 receptor, expressed in sensory neurons, mediates nociceptive, neuropathic, and inflammatory pain, and is enrolled in endometriosis-related pain. Pharmacological inhibition of P2X3 receptor is under evaluation as a pain relief treatment for women with endometriosis. The role of other ATP receptors is also discussed here, e.g., P2X4 and P2X7 receptors, which are involved in inflammatory cell-nerve and microglia-nerve crosstalk, and therefore in inflammatory and neuropathic pain. Adenosine receptors (P1 receptors), by contrast, mainly play antinociceptive and anti-inflammatory roles. Purinome-targeted drugs, including nucleotide receptors and metabolizing enzymes, are potential non-hormonal therapeutic tools for the pharmacological management of endometriosis-related pain.
Topics: Animals; Endometriosis; Female; Humans; Pain; Receptors, Purinergic; Signal Transduction
PubMed: 33198179
DOI: 10.3390/ijms21228512 -
Purinergic Signalling Sep 2021Nucleotide signaling is a key element of the neutrophil activation pathway. Neutrophil recruitment and migration to injured tissues is guided by purinergic receptor... (Review)
Review
Nucleotide signaling is a key element of the neutrophil activation pathway. Neutrophil recruitment and migration to injured tissues is guided by purinergic receptor sensitization, mostly induced by extracellular adenosine triphosphate (ATP) and its hydrolysis product, adenosine (ADO), which is primarily produced by the CD39-CD73 axis located at the neutrophil cell surface. In inflammation unrelated to cancer, neutrophil activation via purinergic signaling aims to eliminate antigens and promote an immune response with minimal damage to healthy tissues; however, an antagonistic response may be expected in tumors. Indeed, alterations in purinergic signaling favor the accumulation of extracellular ATP and ADO in the microenvironment of solid tumors, which promote tumor progression by inducing cell proliferation, angiogenesis, and escape from immune surveillance. Since neutrophils and their N1/N2 polarization spectrum are being considered new components of cancer-related inflammation, the participation of purinergic signaling in pro-tumor activities of neutrophils should also be considered. However, there is a lack of studies investigating purinergic signaling in human neutrophil polarization and in tumor-associated neutrophils. In this review, we discussed the human neutrophil response elicited by nucleotides in inflammation and extrapolated its behavior in the context of cancer. Understanding these mechanisms in cancerous conditions may help to identify new biological targets and therapeutic strategies, particularly regarding tumors that are refractory to traditional chemo- and immunotherapy.
Topics: Animals; Humans; Neoplasms; Neutrophils; Nucleotides; Receptors, Purinergic; Signal Transduction
PubMed: 33913070
DOI: 10.1007/s11302-021-09786-7 -
Current Vascular Pharmacology 2016Purinergic signalling is involved in the control of vascular tone and remodelling. Endothelial cells release purines and pyrimidines in response to changes in blood flow... (Review)
Review
Purinergic signalling is involved in the control of vascular tone and remodelling. Endothelial cells release purines and pyrimidines in response to changes in blood flow (evoking shear stress) and hypoxia. They then act on P2Y, P2X and P1 receptors on endothelial cells leading to release of EDRF mediated by nitric oxide and prostaglandins and EDHF, resulting in vasodilatation. The therapeutic potential of purinergic compounds for the treatment of vascular diseases, including hypertension, ischaemia, atherosclerosis, migraine and coronary artery and diabetic vascular disease as well as vasospasm is discussed.
Topics: Animals; Endothelium, Vascular; Humans; Hypertension; Ischemia; Purines; Receptors, Purinergic; Signal Transduction; Vasoconstriction; Vasodilation
PubMed: 26638799
DOI: 10.2174/1570161114666151202204948 -
Biological & Pharmaceutical Bulletin 2021The purine nucleotide ATP is a fundamental unit in cellular energy metabolism. Extracellular ATP and its metabolites are also ligands for a family of receptors, known as... (Review)
Review
The purine nucleotide ATP is a fundamental unit in cellular energy metabolism. Extracellular ATP and its metabolites are also ligands for a family of receptors, known as purinergic receptors, which are expressed ubiquitously in almost every cell type. In the immune system, extracellular ATP and its signals regulate the migration and activation of immune cells to orchestrate the induction and resolution of inflammation. In this review, we provide an overview of purinergic receptors and their downstream signaling related to macrophage activation. We also discuss the roles of purinergic signaling for macrophage functions in physiological and pathological conditions.
Topics: Adenosine Triphosphate; Animals; Humans; Inflammation; Macrophages; Receptors, Purinergic
PubMed: 33952816
DOI: 10.1248/bpb.b20-00831