scholarly journals In Memoriam Geoffrey Burnstock: Creator of Purinergic Signaling

Function ◽  
2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Alexei Verkhratsky ◽  
Herbert Zimmermann ◽  
Maria P Abbracchio ◽  
Peter Illes ◽  
Francesco DiVirgilio

Abstract Geoff Burnstock (1929–2020) discovered purinergic signaling in a fastidious research that started in early 1960 and culminated in a concept of purinergic nerves in 1972. Subsequently, Geoff developed the concept of purinergic transmission and demonstrated ATP storage, release, and degradation in the context of cotransmission, which was another fundamental concept developed by him. Purinergic transmission contributes to the most fundamental physiological functions such as sensory transduction, regulation of heart rate, smooth muscle contraction, bile secretion, endocrine regulation, immune responses, as well as to various pathophysiological conditions, including inflammation, cancer, neuropathic pain, diabetes, and kidney failure.


Author(s):  
Niemat Ahmed El-Amin Eljabri ◽  
Ahmed Khalil Ahmed ◽  
Awatif Ahmed

The effect of 100 and 50 mg/kg body weight Tribulus terrestris aqueous extract at on the cardiovascular system of rats was studied. Initial heart rate of 160, systolic100 & diastolic 40was considered as normal pressure.. One minute after extract administration the blood pressure and heart rate of rats were raised. The rats' blood pressure continued in a remarkable increasing manner reaching a 180 systolic, 150 diastolic mm/Hg and the heart rate beat were 200, no mortality was observed. Perfusion pressure was raised with the aqueous extract administration then reduced to the normal level after 90 minutes. It was concluded that aqueous extracts of Tribulus terrestris possess significant hypotensive activity in hypertensive rats. The hypotensive effects of Tribulus terrestris appeared may be due to the direct arterial smooth muscle contraction and membrane hypo polarization. These results suggested the curative effect of T. terrestris aqueous extract on hypertensive animals.



2021 ◽  
Vol 12 ◽  
Author(s):  
Shanu Jain ◽  
Kenneth A. Jacobson

Extracellular nucleosides and nucleotides activate a group of G protein-coupled receptors (GPCRs) known as purinergic receptors, comprising adenosine and P2Y receptors. Furthermore, purinergic P2X ion channels are activated by ATP. These receptors are expressed in liver resident cells and play a critical role in maintaining liver function. In the normal physiology, these receptors regulate hepatic metabolic processes such as insulin responsiveness, glycogen and lipid metabolism, and bile secretion. In disease states, ATP and other nucleotides serve as danger signals and modulate purinergic responses in the cells. Recent studies have demonstrated that purinergic receptors play a significant role in the development of metabolic syndrome associated non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), fibrosis, hepatocellular carcinoma (HCC) and liver inflammation. In this concise review, we dissect the role of purinergic signaling in different liver resident cells involved in maintaining healthy liver function and in the development of the above-mentioned liver pathologies. Moreover, we discuss potential therapeutic strategies for liver diseases by targeting adenosine, P2Y and P2X receptors.



Author(s):  
Guy Rousseau

It was in 1972 that Burnstock laid the foundation of a new nerve type that he called ‘purinergic nerves’. In this article, he presented experimental data using five criteria to establish that adenosine triphosphate can be considered to be a neurotransmitter, including (1) the release of a purinergic molecule from terminal axons, (2) the structures of purinergic nerves, (3) the electrophysiological properties of purinergic transmission, (4) the pharmacology of adenyl compounds and purinergic transmission, and (5) the distribution and evolution of the purinergic nerves. However, in spite of convincing data, it took more than 20 years for the scientific community to accept this hypothesis. Since then, it has been recognized that the purinergic system is involved in multiple short-term actions such as cell proliferation and pain.



2019 ◽  
Vol 20 (3) ◽  
pp. 528 ◽  
Author(s):  
Marta Vuerich ◽  
Rasika Harshe ◽  
Simon Robson ◽  
Maria Longhi

Exact causes for autoimmune diseases remain unclear and no cures are available. Breakdown of immunotolerance could set the stage for unfettered immune responses that target self-antigens. Impaired regulatory immune mechanisms could have permissive roles in autoreactivity. Abnormal regulatory immune cell function, therefore, might be a major determinant of the pathogenesis of autoimmune disease. All current treatments are associated with some level of clinical toxicity. Treatment to specifically target dysregulated immunity in these diseases would be a great advance. Extracellular adenosine is a signaling mediator that suppresses inflammation through activation of P1 receptors, most active under pathological conditions. Mounting evidence has linked alterations in the generation of adenosine from extracellular nucleotides by ectonucleotidases, and associated perturbations in purinergic signaling, to the immunological disruption and loss of immunotolerance in autoimmunity. Targeted modulation of the purinergic signaling by either targeting ectonucleotidases or modulating P1 purinergic receptors could therefore restore the balance between autoreactive immune responses; and thereby allow reestablishment of immunotolerance. We review the roles of CD39 and CD73 ectoenzymes in inflammatory states and with the dysregulation of P1 receptor signaling in systemic and organ-specific autoimmunity. Correction of such perturbations could be exploited in potential therapeutic applications.



1992 ◽  
Vol 73 (4) ◽  
pp. 1494-1499 ◽  
Author(s):  
T. J. Verde ◽  
S. G. Thomas ◽  
R. W. Moore ◽  
P. Shek ◽  
R. J. Shephard

Ten elite male runners (age, 29.8 +/- 1.7 yr; maximum oxygen consumption, 65.3 +/- 4.9 ml.kg-1.min-1; 10-km times, 31 min 43 s +/- 1 min 46 s) deliberately increased training schedules by an average of 38% for 3 wk. Resting heart rate and maximal oxygen intake were unchanged, but the heart rate response to acute exercise was decreased. Following heavy training, blood samples taken at rest showed trends to a decreased helper/suppressor cell ratio, an increased phytohemagglutinin (PHA)- and concanavalin (ConA)-stimulated lymphocyte proliferation, and a decreased production of immunoglobulins IgG and IgM. Whereas PHA-stimulated lymphocyte proliferation was initially unchanged by acute exercise, after 3 wk of heavy training the same acute exercise caused an 18% suppression of proliferation. Acute exercise following heavy training did not alter pokeweed-stimulated IgG or IgM synthesis. There was no correlation between changes in lymphocyte subpopulations, helper/suppressor ratios, and mitogen-induced cellular proliferation. The immune system of endurance-trained athletes at rest seemed to tolerate the stress of heavy training, but superimposition of a bout of acute exercise on the chronic stress of heavy training resulted in immunosuppression, which was transient and most likely not of clinical significance.



2012 ◽  
Vol 554-556 ◽  
pp. 1734-1737 ◽  
Author(s):  
Feng Hao ◽  
Zhong Hai Yuan ◽  
Zhi Xin Wang ◽  
Hui Jing Xu ◽  
Fang Fang ◽  
...  

Calcium-activated chloride channels (CaCCs) play pivotal roles in many physiological Activities, including transepithelial fluid secretion, smooth muscle contraction and sensory transduction. TMEM16A is a bona fide calcium-activated chloride channel,which was discovered by three independent labs in 2008 after Calcium-activated chloride channel current was recorded about thirty years ago. In this study, DNA fragments encoding mouse TMEM16A with green fluorescence protein (GFP) fusion protein were subcloned into pcDNA3.1/Zeo. Transient transfection condition was optimized and Fischer Thyroid epithelial cells (FRT) expressing TMEM16A were got by stable transfection. The classical calcium-activated chloride channels current was recorded in FRT cells stably expressing TMEM16A by whole cell patch clamp technique. These results were beneficial for the delving into the effects of other bivalent cations on TMEM16A-CaCCs and the role of TMEM16A-CaCCs in cell proliferation and migration.



PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0254139
Author(s):  
Ashton B. Miller ◽  
Patricia A. Harris ◽  
Virginia D. Barker ◽  
Amanda A. Adams

Long-distance transport is associated with stress-related changes in equine immune function, and shipping-associated illnesses are often reported. Horses are frequently transported short distances, yet the effects of short-term transport on immune function remain largely unknown. Twelve horses, aged 15–30 yr, were assigned to either the control (n = 6) or treatment (n = 6) groups; treatment horses received a daily antioxidant supplement 3 weeks before and after transport. All horses were transported for approximately 1.5–2 hr on Day 0. Blood was collected via jugular venipuncture at 15-min pre- and post-transport and on Days –21, 1, 3, 7, 14, and 21. Body temperature, heart rate, body weight, total cortisol, and gene expression of IFNγ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12α, IL-17α, SAA1, and TNFα in whole blood were measured. Peripheral blood mononuclear cells were isolated, stimulated with PMA/ionomycin, and stained for IFNγ and TNFα before analysis via flow cytometry. Statistical analyses were performed with significance set at P < 0.05 (SAS 9.4). Transport and supplementation did not appear to affect body weight, heart rate, IL-4, IL-8, IL-12α, IL-17α, change (Δ) in the % and mean fluorescence intensity (MFI) of IFNγ+ lymphocytes after stimulation, or Δ in the % and MFI of TNFα+ lymphocytes after stimulation. Supplementation decreased IL-1β and SAA1 expression. Transport increased total cortisol concentration, body temperature, and IL-2, IL-6, and IL-10 expression but decreased IL-1β, TNFα, and IFNγ expression. Short-term transportation affected physiological, endocrine, and immune responses; supplementation may ameliorate inflammation in aged horses. Immune responses were most altered at 15-min post-transport and typically recovered by Day 1, suggesting that horses may be vulnerable to disease during and almost immediately after short-term transport.



2012 ◽  
Vol 22 (5,6) ◽  
pp. 213-219 ◽  
Author(s):  
Mary G. O'Keeffe ◽  
Peter R. Thorne ◽  
Gary D. Housley ◽  
Simon C. Robson ◽  
Srdjan M. Vlajkovic


2014 ◽  
Vol 24 (1) ◽  
pp. 3-3
Author(s):  
Brian Petty, M.A., CCC-SLP
Keyword(s):  




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