Purinergic signalling in the gastrointestinal tract and related organs in health and disease

Burnstock, Geoffrey

doi:10.1007/s11302-013-9397-9

Cited by 93 publications

(102 citation statements)

References 670 publications

(285 reference statements)

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“…Cell‐surface ectonucleotidases (NTPDases) such as NTPDase1 (i.e. CD39), together with the ecto‐5′‐nucleotidase CD73, hydrolyze eATP to adenosine, a purine nucleoside with anti‐inflammatory effects 3, 6, 7. NTPDase1 is present at high levels in intestinal tissues from patients with IBD 8.…”

Section: Introductionmentioning

confidence: 99%

Purine metabolism controls innate lymphoid cell function and protects against intestinal injury

et al. 2018

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Inflammatory bowel disease (IBD) is a condition of chronic inflammatory intestinal disorder with increasing prevalence but limited effective therapies. The purine metabolic pathway is involved in various inflammatory processes including IBD. However, the mechanisms through which purine metabolism modulates IBD remain to be established. Here, we found that mucosal expression of genes involved in the purine metabolic pathway is altered in patients with active ulcerative colitis (UC), which is associated with elevated gene expression signatures of the group 3 innate lymphoid cell (ILC3)–interleukin (IL)‐22 pathway. In mice, blockade of ectonucleotidases (NTPDases), critical enzymes for purine metabolism by hydrolysis of extracellular adenosine 5′‐triphosphate (eATP) into adenosine, exacerbates dextran‐sulfate sodium‐induced intestinal injury. This exacerbation of colitis is associated with reduction of colonic IL‐22‐producing ILC3s, which afford essential protection against intestinal inflammation, and is rescued by exogenous IL‐22. Mechanistically, activation of ILC3s for IL‐22 production is reciprocally mediated by eATP and adenosine. These findings reveal that the NTPDase‐mediated balance between eATP and adenosine regulates ILC3 cell function to provide protection against intestinal injury and suggest potential therapeutic strategies for treating IBD by targeting the purine–ILC3 axis.

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Section: Introductionmentioning

confidence: 99%

Purine metabolism controls innate lymphoid cell function and protects against intestinal injury

et al. 2018

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“…The HH challenge was expected to induce systemic tissue hypoxia, which was confirmed by a substantial decrease in PO 2 in the mixed venous blood, despite no change in the arterial PO 2 (Fig. 2); the tissue hypoxia presumably resulted from a reduction of the blood flow and oxygen delivery to peripheral tissues.…”

Section: Discussionmentioning

confidence: 92%

“…Tissue ischemia is known to activate C-fiber nociceptors in various organ systems including heart, gastrointestinal tract, and skeletal muscles (2,9,20). However, its action on C-fibers in the lung is not known.…”

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confidence: 99%

Hemorrhagic hypotension-induced hypersensitivity of vagal pulmonary C-fibers to chemical stimulation and lung inflation in anesthetized rats

Lin

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Lin RL, Lin YJ, Xu F, Lee LY. Hemorrhagic hypotensioninduced hypersensitivity of vagal pulmonary C-fibers to chemical stimulation and lung inflation in anesthetized rats. Am J Physiol Regul Integr Comp Physiol 308: R605-R613, 2015. First published January 14, 2015 doi:10.1152/ajpregu.00424.2014.-This study was carried out to investigate whether hemorrhagic hypotension (HH) altered the sensitivity of vagal pulmonary C-fibers. The fiber activity (FA) of single vagal pulmonary C-fiber was continuously recorded in anesthetized rats before, during, and after HH was induced by bleeding from the femoral arterial catheter into a blood reservoir and lowering the mean systemic arterial pressure (MSAP) to ϳ40 mmHg for 20 min. Our results showed the following. First, after MSAP reached a steady state of HH, the peak FA response to intravenous injection of capsaicin was elevated by approximately fivefold. The enhanced C-fiber sensitivity continued to increase during HH and sustained even after MSAP returned to baseline during the recovery, but slowly returned to control ϳ20 min later. Second, responses of FA to intravenous injections of other chemical stimulants of pulmonary C-fibers (phenylbiguanide, lactic acid, and adenosine) and a constantpressure lung hyperinflation were all significantly potentiated by HH. Third, infusion of sodium bicarbonate alleviated the systemic acidosis during HH, and it also attenuated, but did not completely prevent, the HH-induced C-fiber hypersensitivity. In conclusion, the pulmonary C-fiber sensitivity was elevated during HH, probably caused by the endogenous release of chemical substances (e.g., lactic acid) that were produced by tissue ischemia during HH. This enhanced C-fiber sensitivity may heighten the pulmonary protective reflexes mediated through these afferents (e.g., cough, J reflex) during hemorrhage when the body is more susceptible to other hazardous insults and pathophysiological stresses.hemorrhage; pulmonary; C-fiber; hypoxia; hypersensitivity VAGAL BRONCHOPULMONARY C-fibers represent ϳ75% of the vagal afferents arising from the lung and airways (17). These unmyelinated afferents innervate the entire respiratory tract and play an important role in regulating the respiratory functions under various physiological and pathophysiological conditions (5, 21). Activation of these afferents elicits centrally mediated protective reflex responses via the cholinergic pathway, which include laryngeal closure, bronchoconstriction and airway hypersecretion, accompanied by cough, airway irritation, dyspneic sensation, and J reflex (5, 21). Activation of these sensory nerves can also trigger release of tachykinins and calcitonin gene-related peptide from the sensory terminals, which can act on a number of effector cells in the respiratory tract (e.g., smooth muscles, cholinergic ganglia, mucous glands, immune cells), and elicit the local "axon reflexes" such as bronchoconstriction, protein extravasation, and inflammatory cell chemotaxis (5, 18, 21).Tissue ischemia is known to activate C-fib...

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“…Purinoceptors are present in all peripheral tissues, being involved in short-term as well as long-term regulation of different functions, including neuromuscular and synaptic transmission and secretion in gut [35], and secretion in kidneys [36], liver [37] and reproductive systems [38]. In vascular [16] and respiratory systems, ATP mediates reflex activities via activation of sensory nerves [39].…”

Section: Introductionmentioning

confidence: 99%

Short- and long-term (trophic) purinergic signalling

Burnstock¹

2016

Phil. Trans. R. Soc. B

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There is long-term (trophic) purinergic signalling involving cell proliferation, differentiation, motility and death in the development and regeneration of most systems of the body, in addition to fast purinergic signalling in neurotransmission, neuromodulation and secretion. It is not always easy to distinguish between short-and long-term signalling. For example, adenosine triphosphate (ATP) can sometimes act as a short-term trigger for long-term trophic events that become evident days or even weeks after the original challenge. Examples of short-term purinergic signalling during sympathetic, parasympathetic and enteric neuromuscular transmission and in synaptic transmission in ganglia and in the central nervous system are described, as well as in neuromodulation and secretion. Long-term trophic signalling is described in the immune/defence system, stratified epithelia in visceral organs and skin, embryological development, bone formation and resorption and in cancer. It is likely that the increase in intracellular Ca 2þ in response to both P2X and P2Y purinoceptor activation participates in many short-and long-term physiological effects. This article is part of the themed issue 'Evolution brings Ca 2þ and ATP together to control life and death'.

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Purinergic signalling in the gastrointestinal tract and related organs in health and disease

Cited by 93 publications

References 670 publications

Purine metabolism controls innate lymphoid cell function and protects against intestinal injury

Purine metabolism controls innate lymphoid cell function and protects against intestinal injury

Hemorrhagic hypotension-induced hypersensitivity of vagal pulmonary C-fibers to chemical stimulation and lung inflation in anesthetized rats

Short- and long-term (trophic) purinergic signalling

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