scholarly journals Purinergic receptor detection in human embryonic epidermis

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Hydar Muhsin Khalfa ◽  
Adnan Albideri ◽  
Haider Salih Jaffat
Keyword(s):  
Purinergic Receptors ◽  
Purinergic Receptor ◽  
Single Layer ◽  
Adenosine Diphosphate ◽  
High Rate ◽  
Sweat Glands ◽  
Purinergic Signalling ◽  
Stem Cell Markers ◽  
Skin Development ◽  
Proliferation And Differentiation

The integumentary system covers the surface of the embryo (skin) and its specialized skin structures including hair, nails, sweat glands, mammary glands and teeth. During fetal skin development, the epidermis changes from a single layer of ectodermal cells at 7–8 days of gestation into a more apparent stratified, keratinized epithelium at 22–24 weeks. Skin development is driven by the complex inter-play between intrinsic and extrinsic pathways. There has been significant interest in determining the molecular cues that regulate the proliferation of human epidermal cells.P2Y receptors are membrane bound G protein coupled receptors. Purinergic signalling mediated by nucleotides such as Adenosine Triphosphate (ATP) and Adenosine Diphosphate (ADP) has also been shown to play a significant role in embryogenesis. Aim:The aim of the study is to identify the presence of purinergic receptors P2Y1,P2Y2,and P2Y4 during human embryonic epidermis development. The expression of purinergic receptors is examined in various anatomical sites and embryonic stages. Human embryonic samples were obtained from fully informed,consenting patients undergoing spontaneous terminations of pregnancy from emergency department at Al-Hilla maternity. Anatomical Sites included abdomen,forehead,back and feet sole. A total of 15 embryos aged between 2-3 months were used for this study. Fresh tissues were sectioned using a freezing cryostat. Tissues were sectioned at 5µm in -24°C and collected on microscopic slides. Slides were allowed to air dry for 30 min prior to immunohistochemical processing. Our study shows strong positivestaining for purinergic receptors P2Y1,P2Y2,and P2Y4 in all selected anatomical sites. Immunohistochemical staining increases with gestational development in all selected anatomical sites. A strong expression of purinergic receptors is seen in anatomical areas which possess high rate of development and strong differentiation rate.purinergic receptors as stem cell markers are actively seen in human epidermis histogeneis and development. Their role is important is epidermal layer proliferation and differentiation.

Cytological and Histological Study of Adult and Neonate Epidermis in Thick and Thin Skin of Various Anatomical Sites

2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Hydar Muhsin Khalfa ◽  
Adnan Albideri ◽  
Haider Salih Jaffat
Keyword(s):  
Histological Study ◽  
Single Layer ◽  
Sweat Glands ◽  
Anatomical Site ◽  
Basal Cells ◽  
Histological Changes ◽  
Mature Adult ◽  
Skin Development ◽  
Stage Of Development ◽  
Thin Skin

The integumentary system covers the surface of the embryo (skin) and its specialized skin structures including hair, nails, sweat glands, mammary glands and teeth. During fetal skin development, the epidermis changes from a single layer of ectodermal cells at 7–8 days of gestation into a more apparent stratified, keratinized epithelium at 22–24 weeks. The aim of the study is to identify the histological and cytological changes that take place during neonatal and adult epidermis development. Human neonatal and adult samples were obtained from fully informed, consenting parent or releatives from Al-hilla mortary / Iraq. Neonatal samples were obtained from neonates after sudden deaths from maternity wards. Anatomical Sites included abdomen, forehead, back, shoulder and feet sole. A totoal of 15 neonates and 10 mature adults were used for this study. Fresh tissues were sectioned using a freezing cryostat. Tissues were sectioned at 5µm in -24°C and collected on microscopic slides. Slides were allowed to air dry for 30 min prior to hematoxyline and eosin staining. Tissues were also photographed using scanning electron microscopy SEM. Cytological measurements were taken using image j software and data was analysed using graph prism. Various cytological and histological changes takes place during neonatal and adult and epidermis development. Our study shows the stages of fair follicule formation as well as number of nucleated layers present at each stage of development and at different anatomical sites. Major histological changes takes places during the transition frm a neonate to a mature adult including the number of basal cells and epidermal thickness depending on the anatomical site.

scholarly journals Purinergic signalling in the cardiovascular system—a tribute to Geoffrey Burnstock

2020 ◽  
Author(s):  
Vera Ralevic
Keyword(s):  
Developmental Biology ◽  
Cardiovascular System ◽  
Scientific Community ◽  
Purinergic Receptors ◽  
Purinergic Receptor ◽  
Purinergic Signalling ◽  
International Scientific Community ◽  
Research Fellow ◽  
System A ◽  
Postdoctoral Research

AbstractGeoffrey Burnstock made groundbreaking discoveries on the physiological roles of purinergic receptors and led on P2 purinergic receptor classification. His knowledge, vision and leadership inspired and influenced the international scientific community. I had the privilege of spending over 10 years (from 1985) with Geoff at the Department of Anatomy and Developmental Biology, initially as a PhD student and then as a postdoctoral research fellow. I regarded him with enormous admiration and affection. This review on purinergic signalling in the cardiovascular system is a tribute to Geoff. It includes some personal recollections of Geoff.

scholarly journals Inflammasomes and the Maintenance of Hematopoietic Homeostasis: New Perspectives and Opportunities

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 309
Author(s):  
Lijing Yang ◽  
Mengjia Hu ◽  
Yukai Lu ◽  
Songling Han ◽  
Junping Wang
Keyword(s):  
Purinergic Receptors ◽  
Therapeutic Potential ◽  
Inflammasome Activation ◽  
Hematopoietic Stem ◽  
Hematopoietic Transplantation ◽  
Proliferation And Differentiation ◽  
Extracellular Stimuli ◽  
Transplantation Complications ◽  
Underlying Mechanisms

Hematopoietic stem cells (HSCs) regularly produce various blood cells throughout life via their self-renewal, proliferation, and differentiation abilities. Most HSCs remain quiescent in the bone marrow (BM) and respond in a timely manner to either physiological or pathological cues, but the underlying mechanisms remain to be further elucidated. In the past few years, accumulating evidence has highlighted an intermediate role of inflammasome activation in hematopoietic maintenance, post-hematopoietic transplantation complications, and senescence. As a cytosolic protein complex, the inflammasome participates in immune responses by generating a caspase cascade and inducing cytokine secretion. This process is generally triggered by signals from purinergic receptors that integrate extracellular stimuli such as the metabolic factor ATP via P2 receptors. Furthermore, targeted modulation/inhibition of specific inflammasomes may help to maintain/restore adequate hematopoietic homeostasis. In this review, we will first summarize the possible relationships between inflammasome activation and homeostasis based on certain interesting phenomena. The cellular and molecular mechanism by which purinergic receptors integrate extracellular cues to activate inflammasomes inside HSCs will then be described. We will also discuss the therapeutic potential of targeting inflammasomes and their components in some diseases through pharmacological or genetic strategies.

Increased susceptibility of purinergic receptor-deficient mice to lung infection withPseudomonasaeruginosa

2005 ◽  
Vol 289 (5) ◽  
pp. L890-L895 ◽  
Author(s):  
Cara Geary ◽  
Henry Akinbi ◽  
Tom Korfhagen ◽  
Jean-Etienne Fabre ◽  
Richard Boucher ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Purinergic Receptors ◽  
Tissue Injury ◽  
Purinergic Receptor ◽  
Intratracheal Instillation ◽  
Lavage Fluid ◽  
Sublethal Dose ◽  
Wild Type ◽  
Double Knockout

Purinergic receptors are expressed throughout the respiratory system in diverse cell types. The efficiency of mucus clearance in the airways, the cascade leading to tissue injury, and inflammation are modulated by autocrine/paracrine release of nucleotides and signaling by purinergic receptors. We assessed the role of purinergic receptors in innate host defense of the lung in vivo by infecting mice deficient in P2Y1, P2Y2, or both receptors with intratracheal instillation of Pseudomonas aeruginosa. After P. aeruginosa challenge, all double knockout (P2Y1/P2Y2−/−) mice succumbed within 30 h of challenge, whereas 85% of the wild-type mice survived. Thirty-three percent of wild-type mice survived beyond 96 h. Single knockout mice, P2Y1−/−, or P2Y2−/−, exhibited intermediate survivals. Twenty-four hours following intratracheal instillation of a sublethal dose of P. aeruginosa, the level of total protein in bronchoalveolar lavage fluid was 1.8-fold higher in double knockout than in wild-type mice ( P < 0.04). Total cell count in bronchoalveolar lavage fluids at 4 h and levels of IL-6 and macrophage inflammatory protein-2 in lung homogenates at 24 h postchallenge were significantly reduced in P2Y1/P2Y2−/− mice relative to wild-type mice. These findings suggest that purinergic receptors exert a protective role against infection of the lungs by P. aeruginosa by decreasing protein leak and enhancing proinflammatory cytokine response.

Adenosine nucleotides in bile

1996 ◽  
Vol 270 (2) ◽  
pp. G246-G252 ◽  
Author(s):  
R. S. Chari ◽  
S. M. Schutz ◽  
J. E. Haebig ◽  
G. H. Shimokura ◽  
P. B. Cotton ◽  
...  
Keyword(s):  
Purinergic Receptors ◽  
Purinergic Receptor ◽  
Receptor Activation ◽  
Hepatoma Cells ◽  
Human Bile ◽  
Nucleotide Release ◽  
Cholangiocarcinoma Cell ◽  
Adenosine Nucleotides ◽  
Vitro Model

Activation of purinergic receptors by ATP stimulates Cl- efflux in biliary epithelial cells. To determine whether purinergic agonists are present under physiological conditions, we have assayed mammalian bile for nucleotides and assessed whether hepatoma and cholangiocarcinoma cell lines are capable of nucleotide release. Bile samples were collected from human, rat, and pig donors and assayed for nucleotide concentrations by luminometry. ATP, ADP, and AMP were present in bile from each species, and the average total nucleotide concentration in human bile was 5.21 +/- 0.91 microM (n = 16). In an in vitro model of HTC rat hepatoma cells or Mz-ChA-1 cholangiocarcinoma cells on a superfused column, nucleotides were present in the effluent from each cell type. Addition of alpha, beta-methyleneadenosine 5'-diphosphate (50 microM) to inhibit 5'-nucleotidase activity increased AMP concentrations two- to threefold. Exposure to forskolin (100 microM) or ionomycin (2 microM) stimulated nucleotide release from cholangiocarcinoma but not hepatoma cells. These studies indicate that adenosine nucleotides are present in bile in concentrations sufficient to activate purinergic receptors. Purinergic receptor activation by local nucleotide release might constitute an autocrine and/or paracrine mechanism for modulation of biliary secretion.

scholarly journals The Impact of Cold Storage on Adenosine Diphosphate-Mediated Platelet Responsiveness

TH Open ◽  
2020 ◽  
Vol 04 (03) ◽  
pp. e163-e172
Author(s):  
Juergen Koessler ◽  
Philipp Klingler ◽  
Marius Niklaus ◽  
Katja Weber ◽  
Angela Koessler ◽  
...  
Keyword(s):  
Cold Storage ◽  
Whole Blood ◽  
Room Temperature ◽  
Purinergic Receptor ◽  
Adenosine Diphosphate ◽  
Receptor Expression ◽  
Activation Markers ◽  
Inhibitory Pathways ◽  
The Impact ◽  
Induced Aggregation

Abstract Introduction Cold storage of platelets is considered to contribute to lower risk of bacterial growth and to more efficient hemostatic capacity. For the optimization of storage strategies, it is required to further elucidate the influence of refrigeration on platelet integrity. This study focused on adenosine diphosphate (ADP)-related platelet responsiveness. Materials and Methods Platelets were prepared from apheresis-derived platelet concentrates or from peripheral whole blood, stored either at room temperature or at 4°C. ADP-induced aggregation was tested with light transmission. Activation markers, purinergic receptor expression, and P2Y12 receptor function were determined by flow cytometry. P2Y1 and P2X1 function was assessed by fluorescence assays, cyclic nucleotide concentrations by immunoassays, and vasodilator-stimulated phosphoprotein (VASP)-phosphorylation levels by Western blot analysis. Results In contrast to room temperature, ADP-induced aggregation was maintained under cold storage for 6 days, associated with elevated activation markers like fibrinogen binding or CD62P expression. Purinergic receptor expression was not essentially different, whereas P2Y1 function deteriorated rapidly at cold storage, but not P2Y12 activity. Inhibitory pathways of cold-stored platelets were characterized by reduced responses to nitric oxide and prostaglandin E1. Refrigeration of citrated whole blood also led to the attenuation of induced inhibition of platelet aggregation, detectable within 24 hours. Conclusion ADP responsiveness is preserved under cold storage for 6 days due to stable P2Y12 activity and concomitant disintegration of inhibitory pathways enabling a higher reactivity of stored platelets. The ideal storage time at cold temperature for the highest hemostatic effect of platelets should be evaluated in further studies.

ATP induces contraction of cultured brain capillary pericytes, via activation of P2Y type purinergic receptors

2020 ◽  
Author(s):  
Sofie Hørlyck ◽  
Changsi Cai ◽  
Hans C Helms ◽  
Martin Lauritzen ◽  
Birger Brodin
Keyword(s):  
Intracellular Calcium ◽  
Purinergic Receptors ◽  
Calcium Release ◽  
Purinergic Receptor ◽  
Cytosolic Calcium ◽  
Receptor Activation ◽  
Confocal Imaging ◽  
Inositol Triphosphate ◽  
Brain Capillary

Brain capillary pericytes have been suggested to play a role in the regulation of cerebral blood-flow under physiological and pathophysiological conditions. ATP has been shown to cause constriction of capillaries under ischemic conditions and suggested to be involved in the "no-reflow" phenomenon. In order to investigate the effects of extracellular ATP on pericyte cell contraction, we studied purinergic receptor activation of cultured bovine brain capillary pericytes. We measured [Ca2+]i-responses to purinergic agonists with the fluorescent indicators fura-2 and Cal-520 and estimated contraction of pericytes as relative change in cell area, using real-time confocal imaging. Addition of ATP caused an increase in cytosolic calcium and contraction of the brain capillary pericytes, both reversible and inhibited by a purinergic receptor antagonist PPADS. Furthermore, we demonstrated that ATP-induced contraction could be eliminated by intracellular calcium-chelation with BAPTA, indicating that the contraction was mediated via purinergic P2 -type receptor-mediated [Ca2+]i-signaling. ATP stimulation induced inositol triphosphate signaling, consistent with the notion of P2Y receptor activation. Receptor profiling studies demonstrated presence of P2Y1 and P2Y2 receptors, using ATP, UTP, ADP and the subtype specific agonists MRS2365 (P2Y1) and 2-thio-UTP (P2Y2)). Addition of specific P2X agonists only caused a [Ca2+]i increase at high concentrations, attributed to activation of inositol triphosphate signaling. Our results suggest that contraction of brain capillary pericytes in vitro by activation of P2Y type purinergic receptors is caused by intracellular calcium release. This adds more mechanistic understanding to the role of pericytes in vessel constriction, and points towards P2Y receptors as potential therapeutic targets.

scholarly journals P2Y1 and P2Y13 purinergic receptors mediate Ca2+ signaling and proliferative responses in pulmonary artery vasa vasorum endothelial cells

2011 ◽  
Vol 300 (2) ◽  
pp. C266-C275 ◽  
Author(s):  
Taras Lyubchenko ◽  
Heather Woodward ◽  
Kristopher D. Veo ◽  
Nana Burns ◽  
Hala Nijmeh ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Purinergic Receptors ◽  
Purinergic Receptor ◽  
Extracellular Atp ◽  
Vasa Vasorum ◽  
Receptor Subtypes ◽  
Extracellular Nucleotide ◽  
Selective Antagonist ◽  
Intracellular Ca

Extracellular ATP and ADP have been shown to exhibit potent angiogenic effects on pulmonary artery adventitial vasa vasorum endothelial cells (VVEC). However, the molecular signaling mechanisms of extracellular nucleotide-mediated angiogenesis remain not fully elucidated. Since elevation of intracellular Ca2+ concentration ([Ca2+]i) is required for cell proliferation and occurs in response to extracellular nucleotides, this study was undertaken to delineate the purinergic receptor subtypes involved in Ca2+ signaling and extracellular nucleotide-mediated mitogenic responses in VVEC. Our data indicate that stimulation of VVEC with extracellular ATP resulted in the elevation of [Ca2+]i via Ca2+ influx through plasma membrane channels as well as Ca2+ mobilization from intracellular stores. Moreover, extracellular ATP induced simultaneous Ca2+ responses in both cytosolic and nuclear compartments. An increase in [Ca2+]i was observed in response to a wide range of purinergic receptor agonists, including ATP, ADP, ATPγS, ADPβS, UTP, UDP, 2-methylthio-ATP (MeSATP), 2-methylthio-ADP (MeSADP), and BzATP, but not adenosine, AMP, diadenosine tetraphosphate, αβMeATP, and βγMeATP. Using RT-PCR, we identified mRNA for the P2Y1, P2Y2, P2Y4, P2Y13, P2Y14, P2X2, P2X5, P2X7, A1, A2b, and A3 purinergic receptors in VVEC. Preincubation of VVEC with the P2Y1 selective antagonist MRS2179 and the P2Y13 selective antagonist MRS2211, as well as with pertussis toxin, attenuated at varying degrees agonist-induced intracellular Ca2+ responses and activation of ERK1/2, Akt, and S6 ribosomal protein, indicating that P2Y1 and P2Y13 receptors play a major role in VVEC growth responses. Considering the broad physiological implications of purinergic signaling in the regulation of angiogenesis and vascular homeostasis, our findings suggest that P2Y1 and P2Y13 receptors may represent novel and specific targets for treatment of pathological vascular remodeling involving vasa vasorum expansion.

scholarly journals Purinergic P2X7 Receptor: A Cation Channel Sensitive to Tumor Microenvironment

2019 ◽  
Vol 14 (1) ◽  
pp. 32-38 ◽  
Author(s):  
Giorgia Scarpellino ◽  
Tullio Genova ◽  
Luca Munaron
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
P2x7 Receptor ◽  
Purinergic Receptor ◽  
Purinergic Signalling ◽  
Cancer Therapies ◽  
Cell Functions ◽  
Anti Cancer ◽  
Purinergic P2x7 Receptor ◽  
And Function

Background: Purinergic signalling is involved in several physiological and pathophysiological processes. P2X7 Receptor (P2X7R) is a calcium-permeable ion channel that is gaining interest as a potential therapeutic target for the treatment of different diseases including inflammation, pain, psychiatric disorders and cancer. P2X7R is ubiquitously expressed and sensitive to high ATP levels, usually found in tumor microenvironment. P2X7R regulates several cell functions, from migration to cell death, but its selective contribution to tumor progression remains controversial.Objective:Current review was conducted to check involvement of P2X7R use in cancer treatment.Methods:We review the most recent patents focused on the use of P2X7R in the treatment of cancer.Results:P2X7R is an intriguing purinergic receptor that plays different roles in tumor progression.Conclusion:Powerful strategies able to selectively interfere with its expression and function should reveal helpful in the development of new anti-cancer therapies.

scholarly journals Hypoxia Modulates Platelet Purinergic Signalling Pathways

2019 ◽  
Vol 120 (02) ◽  
pp. 253-261 ◽  
Author(s):  
Gordon G. Paterson ◽  
Jason M. Young ◽  
Joseph A. Willson ◽  
Christopher J. Graham ◽  
Rebecca C. Dru ◽  
...  
Keyword(s):  
High Altitude ◽  
Sea Level ◽  
Platelet Reactivity ◽  
Clinical Importance ◽  
Adenosine Diphosphate ◽  
Purinergic Signalling ◽  
Systematic Assessment ◽  
Vasp Phosphorylation ◽  
The Impact ◽  
Induced Aggregation

Abstract Background Hypoxia resulting from ascent to high-altitude or pathological states at sea level is known to increase platelet reactivity. Previous work from our group has suggested that this may be adenosine diphosphate (ADP)-specific. Given the clinical importance of drugs targeting ADP pathways, research into the impact of hypoxia on platelet ADP pathways is highly important. Methods Optimul aggregometry was performed on plasma from 29 lowland residents ascending to 4,700 m, allowing systematic assessment of platelet reactivity in response to several platelet agonists. Aggregometry was also performed in response to ADP in the presence of inhibitors of the two main ADP receptors, P2Y1 and P2Y12 (MRS2500 and cangrelor, respectively). Phosphorylation of vasodilator-stimulated phosphoprotein (VASP), a key determinant of platelet aggregation, was analysed using the VASPFix assay. Results Hypobaric hypoxia significantly reduced the ability of a fixed concentration of cangrelor to inhibit ADP-induced aggregation and increased basal VASP phosphorylation. However, in the absence of P2Y receptor inhibitors, we did not find evidence of increased platelet sensitivity to any of the agonists tested and found reduced sensitivity to thrombin receptor-activating peptide-6 amide. Conclusion Our results provide evidence of increased P2Y1 receptor activity at high altitude and suggest down-regulation of the P2Y12 pathway through increased VASP phosphorylation. These changes in ADP pathway activity are of potential therapeutic significance to high-altitude sojourners and hypoxic sea level patients prescribed platelet inhibitors and warrant further investigation.

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