scholarly journals Purinergic P1 Receptor

2020 ◽  
Author(s):  
Keyword(s):  
P1 Receptor

Ectonucleotidases in the digestive system: focus on NTPDase3 localization

2011 ◽  
Vol 300 (4) ◽  
pp. G608-G620 ◽  
Author(s):  
Elise G. Lavoie ◽  
Brian D. Gulbransen ◽  
Mireia Martín-Satué ◽  
Elisabet Aliagas ◽  
Keith A. Sharkey ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Digestive System ◽  
Biologically Active ◽  
Extracellular Nucleotides ◽  
Nucleoside Triphosphate ◽  
Intestinal Epithelial ◽  
Functional Roles ◽  
Salivary Gland Cells ◽  
P1 Receptor ◽  
Specific Localization

Extracellular nucleotides and adenosine are biologically active molecules that bind members of the P2 and P1 receptor families, respectively. In the digestive system, these receptors modulate various functions, including salivary, gastric, and intestinal epithelial secretion and enteric neurotransmission. The availability of P1 and P2 ligands is modulated by ectonucleotidases, enzymes that hydrolyze extracellular nucleotides into nucleosides. Nucleoside triphosphate diphosphohydrolases (NTPDases) and ecto-5′-nucleotidase are the dominant ectonucleotidases at physiological pH. While there is some information about the localization of ecto-5′-nucleotidase and NTPDase1 and -2, the distribution of NTPDase3 in the digestive system is unknown. We examined the localization of these ectonucleotidases, with a focus on NTPDase3, in the gastrointestinal tract and salivary glands. NTPDase1, -2, and -3 are responsible for ecto-ATPase activity in these tissues. Semiquantitative RT-PCR, immunohistochemistry, and in situ enzyme activity revealed the presence of NTPDase3 in some epithelial cells in serous acini of salivary glands and mucous acini and duct cells of sublingual salivary glands, in cells from the stratified esophageal and forestomach epithelia, and in some enteroendocrine cells of the gastric antrum. Interestingly, NTPDase2 and ecto-5′-nucleotidase are coexpressed with NTPDase3 in salivary gland cells and stratified epithelia. In the colon, neurons express NTPDase3 and glial cells express NTPDase2. Ca2+ imaging experiments demonstrate that NTPDases regulate P2 receptor ligand availability in the enteric nervous system. In summary, the specific localization of NTPDase3 in the digestive system suggests functional roles of the enzyme, in association with NTPDase2 and ecto-5′-nucleotidase, in epithelial functions such as secretion and in enteric neurotransmission.

scholarly journals Adenosinergic Signaling as a Key Modulator of the Glioma Microenvironment and Reactive Astrocytes

2022 ◽  
Vol 15 ◽  
Author(s):  
Gabriela N. Debom ◽  
Dominique S. Rubenich ◽  
Elizandra Braganhol
Keyword(s):  
Neurotransmitter Release ◽  
Immune Escape ◽  
Tissue Injury ◽  
Purinergic Signaling ◽  
Tumor Aggressiveness ◽  
Key Factor ◽  
P1 Receptor ◽  
Atp Metabolism ◽  
The Central Nervous System ◽  
Brain Homeostasis

Astrocytes are numerous glial cells of the central nervous system (CNS) and play important roles in brain homeostasis. These cells can directly communicate with neurons by releasing gliotransmitters, such as adenosine triphosphate (ATP) and glutamate, into the multipartite synapse. Moreover, astrocytes respond to tissue injury in the CNS environment. Recently, astrocytic heterogeneity and plasticity have been discussed by several authors, with studies proposing a spectrum of astrocytic activation characterized by A1/neurotoxic and A2/neuroprotective polarization extremes. The fundamental roles of astrocytes in communicating with other cells and sustaining homeostasis are regulated by purinergic signaling. In the CNS environment, the gliotransmitter ATP acts cooperatively with other glial signaling molecules, such as cytokines, which may impact CNS functions by facilitating/inhibiting neurotransmitter release. Adenosine (ADO), the main product of extracellular ATP metabolism, is an important homeostatic modulator and acts as a neuromodulator in synaptic transmission via P1 receptor sensitization. Furthermore, purinergic signaling is a key factor in the tumor microenvironment (TME), as damaged cells release ATP, leading to ADO accumulation in the TME through the ectonucleotidase cascade. Indeed, the enzyme CD73, which converts AMP to ADO, is overexpressed in glioblastoma cells; this upregulation is associated with tumor aggressiveness. Because of the crucial activity of CD73 in these cells, extracellular ADO accumulation in the TME contributes to sustaining glioblastoma immune escape while promoting A2-like activation. The present review describes the importance of ADO in modulating astrocyte polarization and simultaneously promoting tumor growth. We also discuss whether targeting of CD73 to block ADO production can be used as an alternative cancer therapy.

P1 Receptor Agonists/Antagonists in Clinical Trials - Potential Drug Candidates of the Future

2019 ◽  
Vol 25 (26) ◽  
pp. 2792-2807 ◽  
Author(s):  
Pobitra Borah ◽  
Satyendra Deka ◽  
Raghu Prasad Mailavaram ◽  
Pran Kishore Deb
Keyword(s):  
Clinical Trials ◽  
Biological Activities ◽  
Therapeutic Agents ◽  
Current Status ◽  
Preclinical Studies ◽  
P1 Receptors ◽  
Drug Candidates ◽  
Wide Range ◽  
P1 Receptor ◽  
Novel Therapeutic

Background: Adenosine mediates various physiological and pathological conditions by acting on its four P1 receptors (A1, A2A, A2B and A3 receptors). Omnipresence of P1 receptors and their activation, exert a wide range of biological activities. Thus, its modulation is implicated in various disorders like Parkinson’s disease, asthma, cardiovascular disorders, cancer etc. Hence these receptors have become an interesting target for the researchers to develop potential therapeutic agents. Number of molecules were designed and developed in the past few years and evaluated for their efficacy in various disease conditions. Objective: The main objective is to provide an overview of new chemical entities which have crossed preclinical studies and reached clinical trials stage following their current status and future prospective. Methods: In this review we discuss current status of the drug candidates which have undergone clinical trials and their prospects. Results: Many chemical entities targeting various subtypes of P1 receptors are patented; twenty of them have crossed preclinical studies and reached clinical trials stage. Two of them viz adenosine and regadenoson are approved by the Food and Drug Administration. Conclusion: This review is an attempt to highlight the current status, progress and probable future of P1 receptor ligands which are under clinical trials as promising novel therapeutic agents and the direction in which research should proceed with a view to come out with novel therapeutic agents.

scholarly journals Modulation of maximal glycogenolysis in perfused rat liver by adenosine and ATP

1991 ◽  
Vol 277 (3) ◽  
pp. 597-602 ◽  
Author(s):  
F Vanstapel ◽  
M Waebens ◽  
P Van Hecke ◽  
C Decanniere ◽  
W Stalmans
Keyword(s):  
Kinase Inhibitor ◽  
Portal Pressure ◽  
Adenosine Kinase ◽  
Phosphorylase Kinase ◽  
Dibutyryl Cyclic Amp ◽  
Eicosanoid Synthesis ◽  
Biphasic Effect ◽  
Maximal Activation ◽  
P1 Receptor ◽  
Rat Livers

Rat livers perfused at constant flow via the portal vein with dibutyryl cyclic AMP produced glucose equivalents at a steady maximal rate (6 mumol/min per g of liver). Addition of adenosine (150 microM) caused a biphasic effect. (i) First, the glycogenolytic rate rose transiently, to a mean peak of 150% of control levels after 2 min. This glycogenolytic burst was reproduced by two P1-receptor agonists, but not by ATP, and was blocked by a P1-antagonist (8-phenyltheophylline), as well as by inhibitors of eicosanoid synthesis (indomethacin, ibuprofen or aspirin). It did not occur in phosphorylase-kinase-deficient livers. The adenosine-induced glycogenolytic burst coincided with moderate and transient changes in portal pressure (+6 cmH2O) and O2 consumption (-20%), but it could not be explained by an increase in cytosolic Pi, since the n.m.r. signal fell precipitously. (ii) Subsequently, the rate of glycogenolysis decreased to one-third of the preadenosine value, in spite of persistent maximal activation of phosphorylase. The decrease could be linked to the decline in cytosolic Pi: both changes were prevented by the adenosine kinase inhibitor 5-iodotubercidin, whereas they were not affected by ibuprofen or 8-phenyltheophylline, and were not reproduced by non-metabolized adenosine analogues. In comparison with adenosine, ATP caused a slower decrease of Pi and of glycogenolysis. The fate of the cytosolic Pi was unclear, especially with administered ATP, which did not increase the n.m.r.-detectable intracellular ATP.

Purine P1 receptor-dependent immunostimulatory effects of antiviral acyclic analogues of adenine and 2,6-diaminopurine

2006 ◽  
Vol 530 (1-2) ◽  
pp. 179-187 ◽  
Author(s):  
Eva Kmoníčková ◽  
Petr Potměšil ◽  
Antonín Holý ◽  
Zdeněk Zídek
Keyword(s):  
P1 Receptor

Adenosine (P1) receptor signalling

1996 ◽  
Vol 39 (3-4) ◽  
pp. 262-268 ◽  
Author(s):  
Bertil B. Fredholm ◽  
Giulia Arslan ◽  
Bj�rn Kull ◽  
Ewa Kontny ◽  
Per Svenningsson
Keyword(s):  
Receptor Signalling ◽  
P1 Receptor

Differential Expression of Adenosine P1 Receptor ADORA1 and ADORA2A Associated with Glioma Development and Tumor-Associated Epilepsy

2016 ◽  
Vol 41 (7) ◽  
pp. 1774-1783 ◽  
Author(s):  
Jun Huang ◽  
Ming-Na Chen ◽  
Juan Du ◽  
Hao Liu ◽  
Yu-Jiao He ◽  
...  
Keyword(s):  
Differential Expression ◽  
P1 Receptor

Hypoxia and P1 receptor activation regulate the high-affinity concentrative adenosine transporter CNT2 in differentiated neuronal PC12 cells

2013 ◽  
Vol 454 (3) ◽  
pp. 437-445 ◽  
Author(s):  
Lorena Medina-Pulido ◽  
Míriam Molina-Arcas ◽  
Carles Justicia ◽  
Eduardo Soriano ◽  
Ferran Burgaya ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Receptor Activation ◽  
Nucleoside Transporter ◽  
Concentrative Nucleoside Transporter ◽  
Adenosine Uptake ◽  
P1 Receptor ◽  
Cell Energy ◽  
Neuronal Pc12 Cells ◽  
Amp Activated Protein Kinase ◽  
Kinase Phosphorylation

Neuronal PC12 cells express the adenosine CNT2 (concentrative nucleoside transporter 2), which is regulated by purinergic P1 receptors and hypoxia/ischaemia. CNT2-dependent adenosine uptake promotes AMPK (AMP-activated protein kinase) phosphorylation. CNT2 may modulate extracellular adenosine and cell energy balance in neuronal tissue.

P1 bacteriophage and tellurite sensitivity in Klebsiella pneumoniae and Escherichia coli

1984 ◽  
Vol 30 (6) ◽  
pp. 830-836 ◽  
Author(s):  
Juan Tomás ◽  
Miguel Regué ◽  
Ramón Parés ◽  
Juan Jofre ◽  
William W. Kay
Keyword(s):  
Escherichia Coli ◽  
Molecular Weight ◽  
Klebsiella Pneumoniae ◽  
Outer Membrane ◽  
Outer Membrane Proteins ◽  
Protein S ◽  
The Other ◽  
E Coli ◽  
P1 Receptor ◽  
Spontaneous Mutants

Klebsiella pneumoniae and Escherichia coli respond inversely toward P1 bacteriophage or [Formula: see text]. Klebsiella pneumoniae is resistant to both antagonists and E. coli is sensitive. However, P1 cmts lysogens (P1 cmts resistant) of K. pneumoniae became sensitive to tellurite and when cured from P1 cmts regained resistance. Escherichia coli spontaneous mutants selected for resistance to either P1 or [Formula: see text] were collaterally resistant to the other. As well, [Formula: see text] enhanced the adsorption of P1 vir to both E. coli and K. pneumoniae. Several outer membrane proteins were enhanced in the K. pneumoniae lysogens and were reduced in E. coli lysogens; one of which was the same molecular weight (77 000) in both bacteria. When partially purified it enhanced the plaque efficiency of P1 vir. Lipopolysaccharide (LPS) from E. coli C600 inactivated P1 vir, but neither the P1 lysogens nor LPS derived from the lysogens inactivated P1 vir. Escherichia coli P1 lysogens produced only heptose-deficient LPS. It is suggested that both LPS and outer membrane protein(s) comprise the P1 receptor. [Formula: see text] may interact with one or both components.

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