Purinergic Signalling in the Central Nervous System

Burnstock, Geoffrey; Verkhratsky, Alexei

doi:10.1007/978-3-642-28863-0_8

Cited by 8 publications

(8 citation statements)

References 1,272 publications

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“…Vesicular release of lysosomes or secretory vesicles, or conductive release via channels such as Maxi anion channels, Volume-regulated anion channels (VRAC), Connexins or Pannexins are the main mechanisms of regulated ATP release in mammalian cells ( Mikolajewicz et al, 2018 ). Pathological ATP spillage also occurs from traumatically damaged cells ( Burnstock and Verkhratskii, 2012 ). Of interest, non-lethal membrane injury has been demonstrated in vivo in several tissues ( McNeil and Steinhardt, 2003 ), including bone ( Yu et al, 2017 ), under physiological conditions.…”

Section: Introductionmentioning

confidence: 99%

Mechanically stimulated ATP release from murine bone cells is regulated by a balance of injury and repair

Mikolajewicz

Zimmermann

Willie

et al. 2018

eLife

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Bone cells sense and actively adapt to physical perturbations to prevent critical damage. ATP release is among the earliest cellular responses to mechanical stimulation. Mechanical stimulation of a single murine osteoblast led to the release of 70 ± 24 amole ATP, which stimulated calcium responses in neighboring cells. Osteoblasts contained ATP-rich vesicles that were released upon mechanical stimulation. Surprisingly, interventions that promoted vesicular release reduced ATP release, while inhibitors of vesicular release potentiated ATP release. Searching for an alternative ATP release route, we found that mechanical stresses induced reversible cell membrane injury in vitro and in vivo. Ca2+/PLC/PKC-dependent vesicular exocytosis facilitated membrane repair, thereby minimizing cell injury and reducing ATP release. Priming cellular repair machinery prior to mechanical stimulation reduced subsequent membrane injury and ATP release, linking cellular mechanosensitivity to prior mechanical exposure. Thus, our findings position ATP release as an integrated readout of membrane injury and repair.

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Section: Introductionmentioning

confidence: 99%

Mechanically stimulated ATP release from murine bone cells is regulated by a balance of injury and repair

Mikolajewicz

Zimmermann

Willie

et al. 2018

eLife

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“…In the urinary tract, the accumulation of GUO and INO following PNP inhibition has a double protective role since it hampers the generation of urotoxic compounds and preserves the anti-inflammatory and protective nucleosides (Liu et al, 2009). As aging positively correlates with extracellular matrix (ECM) remodeling, the role of GDA, which is able to interact with ECM components (Zuccarini et al, 2018a), may be evaluated too.…”

Section: Discussionmentioning

confidence: 99%

Unfolding New Roles for Guanine-Based Purines and Their Metabolizing Enzymes in Cancer and Aging Disorders

et al. 2021

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“…A use case was given by the characterization of suramin and by showing how the system can be used to provide exact quantitative data on agonist and antagonist potencies and specificities. In the future, the identification of side effects of antiepileptic and anti-inflammatory drugs addressing purinergic receptors could be of interest, due to their wide distribution in the nervous system (Burnstock and Verkhratsky 2012 ; Di Virgilio and Vuerich 2015 ; Riquelme et al 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Human neuronal signaling and communication assays to assess functional neurotoxicity

et al. 2020

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Prediction of drug toxicity on the human nervous system still relies mainly on animal experiments. Here, we developed an alternative system allowing assessment of complex signaling in both individual human neurons and on the network level. The LUHMES cultures used for our approach can be cultured in 384-well plates with high reproducibility. We established here high-throughput quantification of free intracellular Ca2+ concentrations [Ca2+]i as broadly applicable surrogate of neuronal activity and verified the main processes by patch clamp recordings. Initially, we characterized the expression pattern of many neuronal signaling components and selected the purinergic receptors to demonstrate the applicability of the [Ca2+]i signals for quantitative characterization of agonist and antagonist responses on classical ionotropic neurotransmitter receptors. This included receptor sub-typing and the characterization of the anti-parasitic drug suramin as modulator of the cellular response to ATP. To exemplify potential studies on ion channels, we characterized voltage-gated sodium channels and their inhibition by tetrodotoxin, saxitoxin and lidocaine, as well as their opening by the plant alkaloid veratridine and the food-relevant marine biotoxin ciguatoxin. Even broader applicability of [Ca2+]i quantification as an end point was demonstrated by measurements of dopamine transporter activity based on the membrane potential-changing activity of this neurotransmitter carrier. The substrates dopamine or amphetamine triggered [Ca2+]i oscillations that were synchronized over the entire culture dish. We identified compounds that modified these oscillations by interfering with various ion channels. Thus, this new test system allows multiple types of neuronal signaling, within and between cells, to be assessed, quantified and characterized for their potential disturbance.

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Purinergic Signalling in the Central Nervous System

Cited by 8 publications

References 1,272 publications

Mechanically stimulated ATP release from murine bone cells is regulated by a balance of injury and repair

Mechanically stimulated ATP release from murine bone cells is regulated by a balance of injury and repair

Unfolding New Roles for Guanine-Based Purines and Their Metabolizing Enzymes in Cancer and Aging Disorders

Human neuronal signaling and communication assays to assess functional neurotoxicity

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