ATP induces intracellular calcium increases and actin cytoskeleton disaggregation via P2x receptors

Piccoli, David A.; Dayanithi, Govindan; Siatka, Christian; Andrés, Míriam; Dufour, Marie-Noëlle; Guillon, Gilles; Mendre, Christiane

doi:10.1054/ceca.2000.0194

Cited by 48 publications

(25 citation statements)

References 28 publications

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“…All these data agree with the assumed role of this receptor in brain repair after inflammation, infarction, or immune insult [8,226,227,253,[261][262][263]. The P2X 7 receptor mediates an increase in membrane permeability, [336] promoting actin disaggregation [264], and leads to rapid cytoskeletal rearrangements such as membrane blebbing and cell lysis [265]. Recently, there is growing evidence for the existence of this receptor-type on brain neurons by single cell reverse transcriptase polymerase chain reaction, immunohistochemistry, and functional investigations at both presynaptic and postsynaptic densities, probably subserving the normal communication between neurons and glial cells [118,255,[266][267][268][269][270][271].…”

Section: Ischemia/hypoxiasupporting

confidence: 80%

P2 receptors and neuronal injury

Franke

Krügel

Illéš

2006

Pflugers Arch - Eur J Physiol

158

121

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Extracellular adenosine 5'-triphosphate (ATP) was proposed to be an activity-dependent signaling molecule that regulates glia-glia and glia-neuron communications. ATP is a neurotransmitter of its own right and, in addition, a cotransmitter of other classical transmitters such as glutamate or GABA. The effects of ATP are mediated by two receptor families belonging either to the P2X (ligand-gated cationic channels) or P2Y (G protein-coupled receptors) types. P2X receptors are responsible for rapid synaptic responses, whereas P2Y receptors mediate slow synaptic responses and other types of purinergic signaling involved in neuronal damage/regeneration. ATP may act at pre- and postsynaptic sites and therefore, it may participate in the phenomena of long-term potentiation and long-term depression of excitatory synaptic transmission. The release of ATP into the extracellular space, e.g., by exocytosis, membrane transporters, and connexin hemichannels, is a widespread physiological process. However, ATP may also leave cells through their plasma membrane damaged by inflammation, ischemia, and mechanical injury. Functional responses to the activation of multiple P2 receptors were found in neurons and glial cells under normal and pathophysiological conditions. P2 receptor-activation could either be a cause or a consequence of neuronal cell death/glial activation and may be related to detrimental and/or beneficial effects. The present review aims at demonstrating that purinergic mechanisms correlate with the etiopathology of brain insults, especially because of the massive extracellular release of ATP, adenosine, and other neurotransmitters after brain injury. We will focus in this review on the most important P2 receptor-mediated neurodegenerative and neuroprotective processes and their beneficial modulation by possible therapeutic manipulations.

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Section: Ischemia/hypoxiasupporting

confidence: 80%

P2 receptors and neuronal injury

Franke

Krügel

Illéš

2006

Pflugers Arch - Eur J Physiol

158

121

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“…53,54 Beyond that, our findings demonstrate that mechanically induced P 2 X 4 activation via ATP release plays a key role for the reorganization of the actin cytoskeleton in podocytes, indicating that mechanical P 2 X 4 activation might be crucial for the pathomechanism leading to hypertension-induced podocyte damage. We found that nonstretched podocytes exhibited a 6% frequency of podocytes with ARCs; this is similar to Endlich and colleagues' study, 47 which reported a frequency of about 15%.…”

Section: Trpc6mentioning

confidence: 59%

Podocyte Purinergic P2X4 Channels Are Mechanotransducers That Mediate Cytoskeletal Disorganization

Forst¹,

Olteanu²,

Mollet

et al. 2016

Journal of the American Society of Nephrology

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Podocytes are specialized, highly differentiated epithelial cells in the kidney glomerulus that are exposed to glomerular capillary pressure and possible increases in mechanical load. The proteins sensing mechanical forces in podocytes are unconfirmed, but the classic transient receptor potential channel 6 (TRPC6) interacting with the MEC-2 homolog podocin may form a mechanosensitive ion channel complex in podocytes. Here, we observed that podocytes respond to mechanical stimulation with increased intracellular calcium concentrations and increased inward cation currents. However, TRPC6-deficient podocytes responded in a manner similar to that of control podocytes, and mechanically induced currents were unaffected by genetic inactivation of TRPC1/3/6 or administration of the broad-range TRPC blocker SKF-96365. Instead, mechanically induced currents were significantly decreased by the specific P2X purinoceptor 4 (P2X 4 ) blocker 5-BDBD. Moreover, mechanical P2X 4 channel activation depended on cholesterol and podocin and was inhibited by stabilization of the actin cytoskeleton. Because P2X 4 channels are not intrinsically mechanosensitive, we investigated whether podocytes release ATP upon mechanical stimulation using a fluorometric approach. Indeed, mechanically induced ATP release from podocytes was observed. Furthermore, 5-BDBD attenuated mechanically induced reorganization of the actin cytoskeleton. Altogether, our findings reveal a TRPC channel-independent role of P2X 4 channels as mechanotransducers in podocytes.

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“…␣␤MeATP (100 M) had much less effect than ATP, and the action of ATP was reversibly abolished by suramin (300 M). Pubill et al (373) have suggested that disaggregation of actin consequent to calcium entry may also play a role. It was proposed that ATP might have a local paracrine action to enhance the release of arginine vasopressin at the level of the neurohypophysis and that the receptor involved most closely resembled the P2X 2 receptor.…”

Section: Exogenous Atpmentioning

confidence: 99%

Molecular Physiology of P2X Receptors

North

2002

Physiological Reviews

2,683

128

3,397

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P2X receptors are membrane ion channels that open in response to the binding of extracellular ATP. Seven genes in vertebrates encode P2X receptor subunits, which are 40–50% identical in amino acid sequence. Each subunit has two transmembrane domains, separated by an extracellular domain (∼280 amino acids). Channels form as multimers of several subunits. Homomeric P2X1, P2X2, P2X3, P2X4, P2X5, and P2X7 channels and heteromeric P2X2/3 and P2X1/5 channels have been most fully characterized following heterologous expression. Some agonists (e.g., αβ-methylene ATP) and antagonists [e.g., 2′,3′- O-(2,4,6-trinitrophenyl)-ATP] are strongly selective for receptors containing P2X1 and P2X3subunits. All P2X receptors are permeable to small monovalent cations; some have significant calcium or anion permeability. In many cells, activation of homomeric P2X7 receptors induces a permeability increase to larger organic cations including some fluorescent dyes and also signals to the cytoskeleton; these changes probably involve additional interacting proteins. P2X receptors are abundantly distributed, and functional responses are seen in neurons, glia, epithelia, endothelia, bone, muscle, and hemopoietic tissues. The molecular composition of native receptors is becoming understood, and some cells express more than one type of P2X receptor. On smooth muscles, P2X receptors respond to ATP released from sympathetic motor nerves (e.g., in ejaculation). On sensory nerves, they are involved in the initiation of afferent signals in several viscera (e.g., bladder, intestine) and play a key role in sensing tissue-damaging and inflammatory stimuli. Paracrine roles for ATP signaling through P2X receptors are likely in neurohypophysis, ducted glands, airway epithelia, kidney, bone, and hemopoietic tissues. In the last case, P2X7 receptor activation stimulates cytokine release by engaging intracellular signaling pathways.

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ATP induces intracellular calcium increases and actin cytoskeleton disaggregation via P2x receptors

Cited by 48 publications

References 28 publications

P2 receptors and neuronal injury

P2 receptors and neuronal injury

Podocyte Purinergic P2X4 Channels Are Mechanotransducers That Mediate Cytoskeletal Disorganization

Molecular Physiology of P2X Receptors

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