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Purinergic Signalling Mar 2023Increasing evidence suggests that both the occurrence and progression of osteoporosis are associated with inflammation, especially in primary osteoporosis. The... (Review)
Review
Increasing evidence suggests that both the occurrence and progression of osteoporosis are associated with inflammation, especially in primary osteoporosis. The maintenance of skeletal homeostasis is dependent on the complex regulation of bone metabolism. Numerous evidence suggested that purinoceptor networks are essential for bone homeostasis. In this review, the relationship between inflammation and the development of osteoporosis and the role of P2X7 receptor (P2X7R) in regulating the dynamic regulation of bone reconstruction were covered. We also discussed how P2X7R regulates the balance between resorption and bone formation by osteoblasts and reviewed the relevance of P2X7R polymorphisms in skeletal physiology. Finally, we analyzed potential targets of P2X7R for osteoporosis.
Topics: Humans; Osteoporosis; Osteoblasts; Bone and Bones; Osteogenesis; Inflammation; Receptors, Purinergic P2X7; Osteoclasts
PubMed: 35106736
DOI: 10.1007/s11302-021-09836-0 -
Purinergic Signalling Dec 2022Within the family of purinergic receptors, the P2X1 receptor is a ligand-gated ion channel that plays a role in urogenital, immune and cardiovascular function.... (Review)
Review
Within the family of purinergic receptors, the P2X1 receptor is a ligand-gated ion channel that plays a role in urogenital, immune and cardiovascular function. Specifically, the P2X1 receptor has been implicated in controlling smooth muscle contractions of the vas deferens and therefore has emerged as an exciting drug target for male contraception. In addition, the P2X1 receptor contributes to smooth muscle contractions of the bladder and is a target to treat bladder dysfunction. Finally, platelets and neutrophils have populations of P2X1 receptors that could be targeted for thrombosis and inflammatory conditions. Drugs that specifically target the P2X1 receptor have been challenging to develop, and only recently have small molecule antagonists of the P2X1 receptor been available. However, these ligands need further biological validation for appropriate selectivity and drug-like properties before they will be suitable for use in preclinical models of disease. Although the atomic structure of the P2X1 receptor has yet to be determined, the recent discovery of several other P2X receptor structures and improvements in the field of structural biology suggests that this is now a distinct possibility. Such efforts may significantly improve drug discovery efforts at the P2X1 receptor.
Topics: Male; Humans; Receptors, Purinergic P2X1; Urinary Bladder; Muscle Contraction; Vas Deferens; Blood Platelets; Receptors, Purinergic P2X; Adenosine Triphosphate
PubMed: 35821454
DOI: 10.1007/s11302-022-09880-4 -
Purinergic Signalling Mar 2023Hypertension is the leading cause of morbidity and mortality globally among all cardiovascular diseases. Purinergic signalling plays a crucial role in hypertension... (Review)
Review
Hypertension is the leading cause of morbidity and mortality globally among all cardiovascular diseases. Purinergic signalling plays a crucial role in hypertension through the sympathetic nerve system, neurons in the brain stem, carotid body, endothelium, immune system, renin-angiotensin system, sodium excretion, epithelial sodium channel activity (ENaC), and renal autoregulation. Under hypertension, adenosine triphosphate (ATP) is released as a cotransmitter from the sympathetic nerve. It mediates vascular tone mainly through P2X1R activation on smooth muscle cells and activation of P2X4R and P2YR on endothelial cells and also via interaction with other purinoceptors, showing dual effects. P2Y1R is linked to neurogenic hypertension. P2X7R and P2Y11R are potential targets for immune-related hypertension. P2X3R located on the carotid body is the most promising novel therapeutic target for hypertension. AR, AR, AR, and P2X7R are all related to renal autoregulation, which contribute to both renal damage and hypertension. The main focus is on the evidence addressing the involvement of purinoceptors in hypertension and therapeutic interventions.
Topics: Humans; Endothelial Cells; Receptors, Purinergic; Synaptic Transmission; Signal Transduction; Hypertension; Adenosine Triphosphate
PubMed: 35181831
DOI: 10.1007/s11302-022-09852-8 -
Laryngo- Rhino- Otologie Nov 2020
Topics: Deafness; Genotype; Hearing Loss; Humans; Mutation; Phenotype; Receptors, Purinergic P2X2
PubMed: 33111290
DOI: 10.1055/a-1217-2307 -
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 -
Purinergic Signalling Mar 2021Purinergic signalling plays important roles in somatosensory and nociceptive transmission in the dorsal horn of the spinal cord under physiological and... (Review)
Review
Purinergic signalling plays important roles in somatosensory and nociceptive transmission in the dorsal horn of the spinal cord under physiological and pathophysiological conditions. Physiologically, ATP mediates excitatory postsynaptic responses in nociceptive transmission in the superficial dorsal horn, and in transmission of innocuous primary afferent inputs in the deep dorsal horn. Additionally, extracellular conversion of ATP to adenosine mediates inhibitory postsynaptic responses from Pacinian corpuscle afferents, and is implicated in analgesia caused by transcutaneous electrical nerve stimulation in humans. In terms of pathological pain, P2X4 receptors de novo expressed on dorsal horn microglia are implicated in pain hypersensitivity following peripheral nerve injury. There is evidence that involvement of such P2X4 receptors is sexually dimorphic, occurring in males but not in females. Thus, the roles of purinergic signalling in physiological and pathological pain processing are complex and remain an ever-expanding field of research.
Topics: Adenosine Triphosphate; Animals; Disease Models, Animal; Humans; Microglia; Neuralgia; Posterior Horn Cells; Receptors, Purinergic; Spinal Cord Dorsal Horn
PubMed: 33169292
DOI: 10.1007/s11302-020-09748-5 -
Brain Research Bulletin Sep 2019Neurogenesis is a process of generating functional neurons, which occurs during embryonic and adult stages in mammals. While neurogenesis during development phase is... (Review)
Review
Neurogenesis is a process of generating functional neurons, which occurs during embryonic and adult stages in mammals. While neurogenesis during development phase is characterized by intensive proliferation activity in all regions of the brain to form the architecture and neural function of the nervous system, adult neurogenesis occurs with less intensity in two brain regions and is involved in the maintenance of neurogenic niches, local repair, memory and cognitive functions in the hippocampus. Taking such differences into account, the understanding of molecular mechanisms involved in cell differentiation in developmental stages and maintenance of the nervous system is an important research target. Although embryonic and adult neurogenesis presents several differences, signaling through purinergic receptors participates in this process throughout life. For instance, while embryonic neurogenesis involves P2X7 receptor down-regulation and calcium waves triggered by P2Y1 receptor stimulation, adult neurogenesis may be enhanced by increased activity of A and P2Y1 receptors and impaired by A, P2Y13 and P2X7 receptor stimulation.
Topics: Adenosine Triphosphate; Animals; Brain; Calcium; Calcium Signaling; Cell Differentiation; Cell Proliferation; Hippocampus; Humans; Nervous System; Neurogenesis; Purines; Receptors, Purinergic; Receptors, Purinergic P2X7; Receptors, Purinergic P2Y1; Signal Transduction
PubMed: 30593881
DOI: 10.1016/j.brainresbull.2018.12.013 -
Purinergic Signalling Dec 2019Extracellular purines (ATP and adenosine) are ubiquitous intercellular messengers. During tissular damage, they function as damage-associated molecular patterns (DAMPs).... (Review)
Review
Extracellular purines (ATP and adenosine) are ubiquitous intercellular messengers. During tissular damage, they function as damage-associated molecular patterns (DAMPs). In this context, purines announce tissue alterations to initiate a reparative response that involve the formation of the inflammasome complex and the recruitment of specialized cells of the immune system. The present review focuses on the role of the purinergic system in liver damage, mainly during the onset and development of fibrosis. After hepatocellular injury, extracellular ATP promotes a signaling cascade that ameliorates tissue alterations to restore the hepatic function. However, if cellular damage becomes chronic, ATP orchestrates an aberrant reparative process that results in severe liver diseases such as fibrosis and cirrhosis. ATP and adenosine, their receptors, and extracellular ectonucleotidases are mediators of unique processes that will be reviewed in detail.
Topics: Adenosine; Adenosine Triphosphate; Animals; Humans; Liver; Liver Diseases; Purines; Receptors, Purinergic
PubMed: 31576486
DOI: 10.1007/s11302-019-09680-3 -
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