Neuronal synthesis, storage and release of ATP

Sperlágh, Beáta; Vizi, Sylvester E.

doi:10.1006/smns.1996.0023

Cited by 99 publications

(73 citation statements)

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“…Interestingly, a similar mechanism of ATP secretion has also been demonstrated in astrocytes [16]. Thus, lysosomal exocytosis may be a general mechanism for ATP release in glial cells, in contrast to that in neurons, where ATP is co-released with other neurotransmitters from synaptic vesicles [34].…”

Section: Discussionmentioning

confidence: 73%

Microglial migration mediated by ATP-induced ATP release from lysosomes

et al. 2012

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Microglia are highly motile cells that act as the main form of active immune defense in the central nervous system. Attracted by factors released from damaged cells, microglia are recruited towards the damaged or infected site, where they are involved in degenerative and regenerative responses and phagocytotic clearance of cell debris. ATP release from damaged neural tissues has been suggested to mediate the rapid extension of microglial process towards the site of injury. However, the mechanisms of the long-range migration of microglia remain to be clarified. Here, we found that lysosomes in microglia contain abundant ATP and exhibit Ca 2+ -dependent exocytosis in response to various stimuli. By establishing an efficient in vitro chemotaxis assay, we demonstrated that endogenously-released ATP from microglia triggered by local microinjection of ATPγS is critical for the long-range chemotaxis of microglia, a response that was significantly inhibited in microglia treated with an agent inducing lysosome osmodialysis or in cells derived from mice deficient in Rab 27a (ashen mice), a small GTPase required for the trafficking and exocytosis of secretory lysosomes. These results suggest that microglia respond to extracellular ATP by releasing ATP themselves through lysosomal exocytosis, thereby providing a positive feedback mechanism to generate a long-range extracellular signal for attracting distant microglia to migrate towards and accumulate at the site of injury.

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Section: Discussionmentioning

confidence: 73%

Microglial migration mediated by ATP-induced ATP release from lysosomes

et al. 2012

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“…Thus, adenosine would be locally generated in the synapse in amounts directly proportional to synaptic activity, and would act through inhibitory A 1 receptors as a feedback mechanism to restraint excessive synaptic activation . Two parallel mechanisms were considered to understand how the levels of synaptic adenosine would parallel synaptic activity: (1) adenosine would be formed extracellularly upon catabolism of released ATP originated from synaptic vesicles (reviewed in Sperlágh and Vizi, 1996); (2) adenosine would be released from the postsynaptic neuron as a consequence of the activation of ionotropic glutamate receptors (see Dunwiddie and Diao, 1994;Mitchell et al, 1993a). Irrespective of the source of synaptic adenosine, the predominance of A 1 receptor-mediated inhibition behaved as a homeostatic 'autocrine'-like role restricted to a particular excitatory synapse.…”

Section: Source Of Endogenous Extracellular Adenosinementioning

confidence: 99%

“…In fact, there is ground to propose that the role of adenosine in the control of synaptic plasticity might not only be limited to the 'paracrine'-like action of inhibitory A 1 receptors, but is supplemented by an 'autocrine'-like role of facilitatory A 2A receptors restricted to activated synapses (reviewed in Ferré et al, 2005). In fact, several studies have shown that stimulated nerve terminals can directly release ATP, which is stored in synaptic vesicles (reviewed in Sperlágh and Vizi, 1996). However, this stimulation-evoked release of ATP from nerve terminals seems to differ from the release of classical neurotransmitters (Farinas et al, 1992;Magalhães-Cardoso et al, 2003;Rabasseda et al, 1987;Santos et al, 1999; see also Coco et al, 2003).…”

Section: Adenosine As a Synaptic Modulator-a 2a Receptorsmentioning

confidence: 99%

Different cellular sources and different roles of adenosine: A1 receptor-mediated inhibition through astrocytic-driven volume transmission and synapse-restricted A2A receptor-mediated facilitation of plasticity

Cunha

2008

Neurochemistry International

149

129

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Adenosine is a prototypical neuromodulator, which mainly controls excitatory transmission through the activation of widespread inhibitory A 1 receptors and synaptically located A 2A receptors. It was long thought that the predominant A 1 receptor-meditated modulation by endogenous adenosine was a homeostatic process intrinsic to the synapse. New studies indicate that endogenous extracellular adenosine is originated as a consequence of the release of gliotransmitters, namely ATP, which sets a global inhibitory tonus in brain circuits rather than in a single synapse. Thus, this neuron-glia long-range communication can be viewed as a form of non-synaptic transmission (a concept introduced by Professor Sylvester Vizi), designed to reduce noise in a circuit. This neuron-glia-induced adenosine release is also responsible for exacerbating salient information through A 1 receptor-mediated heterosynaptic depression, whereby the activation of a particular synapse recruits a neuron-glia network to generate extracellular adenosine that inhibits neighbouring non-tetanised synapses. In parallel, the local activation of facilitatory A 2A receptors by adenosine, formed from ATP released only at high frequencies from neuronal vesicles, down-regulates A 1 receptors and facilitates plasticity selectively in the tetanised synapse. Thus, upon high-frequency firing of a given pathway, the combined exacerbation of global A 1 receptormediated inhibition in the circuit (heterosynaptic depression) with the local synaptic activation of A 2A receptors in the activated synapse, cooperate to maximise salience between the activated and non-tetanised synapses. #

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“…The inner surfaces of smooth muscle organs are covered by a variety of epithelial cells (e.g., vascular endothelium, bladder urothelium, endometrium, airway epithelium, and gastric mucosa) that also contribute to the functional complexity of the smooth muscle wall. Virtually all cell types can release extracellular purines in response to mechanical stretch, cell swelling, inflammatory mediators, action potential firings, receptor activation or smooth muscle contraction (2,4,15). Purine (i.e., ATP) release pathways range from vesicle exocytosis to release through connexin and pannexin channels, P2X7 receptor pores, maxi ion channels, volume-regulated ion channels, and membrane transport (4,6,16).…”

Section: Functional Complexity Of Smooth Musclementioning

confidence: 99%

“…The first claim regarding the identity of the NANC neurotransmitter in smooth muscle was made for ATP in the early 1970s (20). In the following decades evidence was accumulated for the presence of ATP in synaptic and secretory vesicles, co-release of ATP with classical neurotransmitters, presence of P2 receptors on cell membranes, and extracellular metabolism of ATP (5,6,15,19,21). Such findings, although originally obtained in single cell-type systems such as invertebrate motor neurons, cultured neurons, astrocytes, neuroendocrine cells, and isolated brain synaptosomes, have commonly been generalized to complex smooth muscle tissues assigning ATP as the universal purine neurotransmitter.…”

Section: Neurotransmissionmentioning

confidence: 99%

Neuronal and extraneuronal release of ATP and NAD⁺ in smooth muscle

Mutafova‐Yambolieva¹

2012

IUBMB Life

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SUMMARYAdenosine 5′-triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD + ) are key intracellular constituents involved in energy transfer and redox homeostasis in the cell. ATP is also released in the extracellular space and in the past half century it has been assumed to be the purinergic neurotransmitter in many systems including smooth muscle. In some smooth muscles (i.e., the human urinary bladder detrusor muscle) ATP does appear to be primarily released from nerves upon action potential firings, but in other smooth muscles (i.e., the human large intestine) ATP does not mimic the endogenous purine neurotransmitter. It was recently found that NAD + , another ubiquitous intracellular adenine nucleotide, also follows a regulated release in neurosecretory cells, vascular and visceral smooth muscles, and the brain. In some cases NAD + fulfills pre-and postsynaptic criteria for a neurotransmitter better than ATP. Therefore, the purine hypothesis of neural regulation in smooth muscle is in need of reevaluation. This article will briefly review the current understanding of neuronal and extraneuronal release of purines in smooth muscle with emphasis on the roles of extracellular ATP and NAD + , and, further, will discuss more recent information about the likely involvement of multiple purines in smooth muscle neurotransmission.

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Neuronal synthesis, storage and release of ATP

Cited by 99 publications

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Microglial migration mediated by ATP-induced ATP release from lysosomes

Microglial migration mediated by ATP-induced ATP release from lysosomes

Different cellular sources and different roles of adenosine: A1 receptor-mediated inhibition through astrocytic-driven volume transmission and synapse-restricted A2A receptor-mediated facilitation of plasticity

Neuronal and extraneuronal release of ATP and NAD⁺ in smooth muscle

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Neuronal synthesis, storage and release of ATP

Cited by 99 publications

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Microglial migration mediated by ATP-induced ATP release from lysosomes

Microglial migration mediated by ATP-induced ATP release from lysosomes

Different cellular sources and different roles of adenosine: A1 receptor-mediated inhibition through astrocytic-driven volume transmission and synapse-restricted A2A receptor-mediated facilitation of plasticity

Neuronal and extraneuronal release of ATP and NAD+ in smooth muscle

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Neuronal and extraneuronal release of ATP and NAD⁺ in smooth muscle