Receptors for Purines and Pyrimidines

Ralevic, Vera; Burnstock, Geoffrey

doi:10.1007/978-3-642-28863-0_5

Cited by 1,014 publications

(24 citation statements)

References 915 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Suramin is generally selective as an antagonist for P2 receptors versus other types of receptors, but it does not discriminate between P2X and P2Y receptors [47]. In the present study, suramin reversibly inhibited the ATP-induced [Ca 2 + ] i increase by 65% in all tested cells, suggesting that P2 receptors are functional in P7 NPs.…”

Section: Purinergic Receptor Activation In P7 Hesc Npssupporting

confidence: 50%

Plasticity of Calcium Signaling Cascades in Human Embryonic Stem Cell-Derived Neural Precursors

Forostyak

Romanyuk

Verkhratsky

et al. 2013

Stem Cells and Development

Self Cite

View full text Add to dashboard Cite

Human embryonic stem cell-derived neural precursors (hESC NPs) are considered to be a promising tool for cellbased therapy in central nervous system injuries and neurodegenerative diseases. The Ca 2 + ion is an important intracellular messenger essential for the regulation of various cellular functions. We investigated the role and physiology of Ca 2 + signaling to characterize the functional properties of CCTL14 hESC NPs during long-term maintenance in culture (in vitro). We analyzed changes in cytoplasmic Ca

show abstract

Section: Purinergic Receptor Activation In P7 Hesc Npssupporting

confidence: 50%

Plasticity of Calcium Signaling Cascades in Human Embryonic Stem Cell-Derived Neural Precursors

Forostyak

Romanyuk

Verkhratsky

et al. 2013

Stem Cells and Development

Self Cite

View full text Add to dashboard Cite

show abstract

“…The P2X receptor is also called ionotropic and functions as a non-selective cation ion channel. Meanwhile, the P2Y receptor is coupled to G protein and therefore is also called metabotropic (Burnstock and Ralevic 1998 ).…”

Section: Purinergic Receptorsmentioning

confidence: 99%

Ecto-nucleotidases and Ecto-phosphatases from Leishmania and Trypanosoma Parasites

Freitas-Mesquita

Meyer‐Fernandes

2013

Subcellular Biochemistry

View full text Add to dashboard Cite

Ecto-enzymes can be defined as membrane-bound proteins that have their active site facing the extracellular millieu. In trypanosomatids, the physiological roles of these enzymes remain to be completed elucidated; however, many important events have already been related to them, such as the survival of parasites during their complex life cycle and the successful establishment of host infection. This chapter focuses on two remarkable classes of ecto-enzymes: ecto-nucleotidases and ecto-phosphatases, summarizing their occurrence and possible physiological roles in Leishmania and Trypanosoma genera. Ecto-nucleotidases are characterized by their ability to hydrolyze extracellular nucleotides, playing an important role in purinergic signaling. By the action of these ecto-enzymes, parasites are capable of modulating the host immune system, which leads to a successful parasite infection. Furthermore, ecto-nucleotidases are also involved in the purine salvage pathway, acting in the generation of nucleosides that are able to cross plasma membrane via specialized transporters. Another important ecto-enzyme present in a vast number of pathogenic organisms is the ecto-phosphatase. These enzymes are able to hydrolyze extracellular phosphorylated substrates, releasing free inorganic phosphate that can be internalized by the cell, crossing the plasma membrane through a Pi-transporter. Ecto-phosphatases are also involved in the invasion and survival of parasite in the host cells. Several alternative functions have been suggested for these enzymes in parasites, such as participation in their proliferation, differentiation, nutrition and protection. In this context, the present chapter provides an overview of recent discoveries related to the occurrence of ecto-nucleotidase and ecto-phosphatase activities in Leishmania and Trypanosoma parasites.

show abstract

“…P2 receptors are classified into two classes: ionotropic P2X receptors (P2XR) and metabotropic P2Y receptors (P2YR) [1].…”

Section: Introductionmentioning

confidence: 99%

“…IP3 induces an increase of intracellular calcium via IP3R activation in the endoplasmic reticulum. Meanwhile, P2Y12, P2Y13, and P2Y14 subtypes are coupled to Gi-protein and inhibit adenylyl cyclase (AC), causing a decrease in cyclic adenosine monophosphate (cAMP) formation [1,2].…”

Section: Introductionmentioning

confidence: 99%

New Insights in Purinergic Therapy: Novel Antagonists for UTP-Activated P2Y Receptors from Natural Products

Ferreira¹,

Soares‐Bezerra²,

Silveira³

et al. 2018

Preprint

View full text Add to dashboard Cite

P2Y2 and P2Y4 receptors are physiologically activated by UTP and are widely expressed in many cell types in humans. They promote an increase in intracellular calcium via PLCβ/ IP3 and act on ion flux and water secretion. P2Y2 plays an important role in inflammation and proliferation of tumor cells, which could be attenuated with the use of antagonists. However, little is known about the physiological functions related to P2Y4 due to the lack of selective ligands for these receptors, which can be solved through the search of novel compounds with antagonistic activity. In the present study, we have applied a methodology of calcium measurement to identify new antagonist candidates for these receptors. Firstly, we established optimal conditions for calcium assay using J774.G8, a murine macrophage cell line, which expresses functional P2Y2 and P2Y4 receptors. J774.G8 cells were loaded with 2 μM of Fluo-4 to test its sensitivity in responding calcium stimuli. ATP and ionomycin, known as inductors of intracellular calcium rise, were used to stimulate cells. The EC50 obtained were 11 μM and 103 nM, respectively. Subsequently, investigation of P2Y2 and P2Y4 expression was performed. These cells responded with EC50 of 1.021 μM to the UTP stimulation. Screening assays were performed and a total of 100 extracts from Brazilian natural products were tested. JA2, RA3, and RB3 extracts stood out for their ability to inhibit UTP-induced responses without causing cytotoxicity and presented IC50 of 32.32 μg/mL, 14.99 μg/mL, and 12.98 μg/mL, respectively. Collectively, our results point to the discovery of potential antagonists candidates from natural products for UTPactivated receptors.

show abstract

Receptors for Purines and Pyrimidines

Cited by 1,014 publications

References 915 publications

Plasticity of Calcium Signaling Cascades in Human Embryonic Stem Cell-Derived Neural Precursors

Plasticity of Calcium Signaling Cascades in Human Embryonic Stem Cell-Derived Neural Precursors

Ecto-nucleotidases and Ecto-phosphatases from Leishmania and Trypanosoma Parasites

New Insights in Purinergic Therapy: Novel Antagonists for UTP-Activated P2Y Receptors from Natural Products

Contact Info

Product

Resources

About