Diadenosine polyphosphates facilitate the evoked release of acetylcholine from rat hippocampal nerve terminals

Pereira, M. Fátima; Hernández, Miguel Díaz; Pintor, Jesús; Miras-Portugal, Marı́a Teresa; Cunha, Rodrigo A.; Ribeiro, Joaquim A.

doi:10.1016/s0006-8993(00)02726-8

Cited by 9 publications

(7 citation statements)

References 25 publications

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“…), being involved in neurotransmitter/neuromodulatory functions in the nervous system (Pereira et al . ; Oaknin et al . ; Jimenez et al .…”

Section: Discussionmentioning

confidence: 99%

“…Exocytotically released Ap n A interact with specific dinucleotide receptors but the ionotropic P2X, metabotropic P2Y and P1 adenosine receptors may also function as Ap n A targets Hoyle et al 2001). Results obtained using very different experimental approaches support the idea that extracellular Ap n A, acting on P1, P2 or their specific dinucleotide receptors, can effectively modulate neural functions (Pereira et al 2000;Oaknin et al 2001;Jimenez et al 2002;Delicado et al 2006). Moreover, neuroprotective effects against injuries induced by ischemia or 6-hydroxydopamine injection in rat brain have been described for Ap 4 A (Wang et al 2003).…”

mentioning

confidence: 88%

“…Results obtained using very different experimental approaches support the idea that extracellular Ap n A, acting on P1, P2 or their specific dinucleotide receptors, can effectively modulate neural functions (Pereira et al . ; Oaknin et al . ; Jimenez et al .…”

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confidence: 99%

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Ectonucleotide pyrophosphatase/phosphodiesterase activity in Neuro‐2a neuroblastoma cells: changes in expression associated with neuronal differentiation

Gómez‐Villafuertes

Pintor

Miras-Portugal

et al. 2014

Journal of Neurochemistry

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Neuro-2a (N2a) neuroblastoma cells display an ectoenzymatic hydrolytic activity capable of degrading diadenosine polyphosphates. The Ap n A-cleaving activity has been analysed with the use of the fluorogenic compound BODIPY â FL guanosine 5 0 -O-(3-thiotriphosphate) thioester. Hydrolysis of this dinucleotide analogue showed a hyperbolic kinetic with a K m value of 4.9 AE 1.3 lM. Diadenosine pentaphosphate, diadenosine tetraphosphate, diadenosine triphosphate, and the nucleoside monophosphate AMP behaved as an inhibitor of BODIPY â FL guanosine 5 0 -O-(3-thiotriphosphate) thioester extracellular degradation. Ectoenzymatic activity shared the typical characteristics of the ectonucleotide pyrophosphatase/phosphodiesterase family, as hydrolysis reached maximal activity at alkaline pH and was dependent on the presence of divalent cations, being strongly inhibited by EDTA and activated by Zn 2+ ions. Both NPP1 and NPP3 isozymes are expressed in N2a cells, their expression levels substantially changing when cells differentiate into a neuronal-like phenotype. In this sense, it is relevant to point the expression pattern of the NPP3 protein, whose levels were drastically reduced in the differentiated cells, being almost completely absent after 24 h of differentiation. Enzymatic activity assays carried out with differentiated N2a cells showed that NPP1 is the main isozyme involved in the extracellular degradation of dinucleotides in these cells, this enzyme reducing its activity and changing its subcellular location following neuronal differentiation.

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“…), being involved in neurotransmitter/neuromodulatory functions in the nervous system (Pereira et al . ; Oaknin et al . ; Jimenez et al .…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 88%

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Ectonucleotide pyrophosphatase/phosphodiesterase activity in Neuro‐2a neuroblastoma cells: changes in expression associated with neuronal differentiation

Gómez‐Villafuertes

Pintor

Miras-Portugal

et al. 2014

Journal of Neurochemistry

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“…It is to be emphasized that agonistic actions on the presynaptic adenosine A 1 or GABA B receptors, which are coupled to G i /G 0 proteins, induce a significant increase in the affinity of the dinucleotide receptors for its substrates, with EC 50 values in the low nanomolar or even picomolar range, which confers the dinucleotide receptor the capacity to respond to more physiologically relevant Ap n As concentrations [22,23]. Results obtained using very different experimental approaches support the idea that extracellular Ap n As, acting on either P2 or their specific dinucleotide receptors, can effectively modulate neural functions [20,24,25].…”

Section: +mentioning

confidence: 77%

“…permeable channel present in synaptic terminals from different brain areas, whose activation facilitates neurotransmitter release [17][18][19][20]. Presynaptic dinucleotide receptor is under the modulation of protein kinases and protein phosphatases, which depend on second messenger cascades coupled to membrane receptors [21].…”

Section: +mentioning

confidence: 99%

Presence of diadenosine polyphosphates in microdialysis samples from rat cerebellum in vivo: effect of mild hyperammonemia on their receptors

Gualix

Gómez‐Villafuertes

Pintor

et al. 2013

Purinergic Signalling

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Diadenosine triphosphate (Ap 3 A), diadenosine tetraphosphate (Ap 4 A), and diadenosine pentaphosphate (Ap 5 A) have been identified in microdialysis samples from the cerebellum of conscious freely moving rats, under basal conditions, by means of a high-performance liquid chromatography method. The occurrence of Ap 3 A in the cerebellar microdyalisates is noteworthy, as the presence of this compound in the interstitial medium in neural tissues has not been previously described. The concentrations measured for the diadenosine polyphosphates in the cerebellar dialysate were (in nanomolar) 10.5±2.9, 5.4±1.2, and 5.8±1.3 for Ap 3 A, Ap 4 A, and Ap 5 A, respectively. These concentrations are in the range that allows the activation of the presynaptic dinucleotide receptor in nerve terminals. However, a possible interaction of these dinucleotides with other purinergic receptors cannot be ruled out, as rat cerebellum expresses a variety of P2X or P2Y receptors susceptible to be activated by diadenosine polyphosphates, such as the P2X1-4, P2Y 1 , P2Y 2 , P2Y 4 , and P2Y 12 receptors, as demonstrated by quantitative realtime PCR. Also, the ecto-nucleotide pyrophosphatases/ phosphodiesterases NPP1 and NPP3, able to hydrolyze the diadenosine polyphosphates and terminate their extracellular actions, are expressed in the rat cerebellum. All these evidences contribute to reinforce the role of diadenosine polyphosphates as signaling molecules in the central nervous system. Finally, we have analyzed the possible differences in the concentration of diadenosine polyphosphates in the cerebellar extracellular medium and changes in the expression levels of their receptors and hydrolyzing enzymes in an animal model of moderate hyperammonemia.

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Diadenosine tetra- and pentaphosphates affect contractility and bioelectrical activity in the rat heart via P2 purinergic receptors

Pustovit

Kuzmin

Abramochkin

2015

Naunyn-Schmiedeberg's Arch Pharmacol

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Diadenosine polyphosphates (Ap(n)As) are endogenously produced molecules which have been identified in various tissues of mammalian organism, including myocardium. Ap(n)As contribute to the blood clotting and are also widely accepted as regulators of blood vascular tone. Physiological role of Ap(n)As in cardiac muscle has not been completely elucidated. The present study aimed to investigate the effects of diadenosine tetra- (Ap4A) and penta- (Ap5A) polyphosphates on contractile function and action potential (AP) waveform in rat supraventricular and ventricular myocardium. We have also demonstrated the effects of A4pA and Ap5A in myocardial sleeves of pulmonary veins (PVs), which play a crucial role in genesis of atrial fibrillation. APs were recorded with glass microelectrodes in multicellular myocardial preparations. Contractile activity was measured in isolated Langendorff-perfused rat hearts. Both Ap4A and Ap5A significantly reduced contractility of isolated Langendorff-perfused heart and produced significant reduction of AP duration in left and right auricle, interatrial septum, and especially in right ventricular wall myocardium. Ap(n)As also shortened APs in rat pulmonary veins and therefore may be considered as potential proarrhythmic factors. Cardiotropic effects of Ap4A and Ap5A were strongly antagonized by selective blockers of P2 purine receptors suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), while P1 blocker DPCPX was not effective. We conclude that Ap(n)As may be considered as new class of endogenous cardioinhibitory compounds. P2 purine receptors play the central role in mediation of Ap4A and Ap5A inhibitory effects on electrical and contractile activity in different regions of the rat heart.

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Diadenosine polyphosphates facilitate the evoked release of acetylcholine from rat hippocampal nerve terminals

Cited by 9 publications

References 25 publications

Ectonucleotide pyrophosphatase/phosphodiesterase activity in Neuro‐2a neuroblastoma cells: changes in expression associated with neuronal differentiation

Ectonucleotide pyrophosphatase/phosphodiesterase activity in Neuro‐2a neuroblastoma cells: changes in expression associated with neuronal differentiation

Presence of diadenosine polyphosphates in microdialysis samples from rat cerebellum in vivo: effect of mild hyperammonemia on their receptors

Diadenosine tetra- and pentaphosphates affect contractility and bioelectrical activity in the rat heart via P2 purinergic receptors

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