Characterization of diadenosine polyphosphate transport into chromaffin granules from adrenal medulla

Gualix, Javier; Fideu, M. D.; Pintor, J; Rotllán, Pedro; García‐Carmona, Francisco

doi:10.1096/fasebj.11.12.9337151

Cited by 22 publications

(20 citation statements)

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“…ATP transport is driven by Δψ but not by ΔpH and is stimulated in the presence of millimolar order Cl − and partially inhibited by atractyloside [27]. The uptake of fluorescent ATP analogues and diadenosine polyphosphate ( 3 HAp5A) by chromaffin granule ghosts and synaptic vesicles, respectively, has also been reported [28][29][30].…”

Section: Vesicular Storage Of Atpmentioning

confidence: 99%

Vesicular nucleotide transporter (VNUT): appearance of an actress on the stage of purinergic signaling

Moriyama

Hiasa

Sakamoto³

et al. 2017

Purinergic Signalling

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Vesicular storage of ATP is one of the processes initiating purinergic chemical transmission. Although an active transport mechanism was postulated to be involved in the processes, a transporter(s) responsible for the vesicular storage of ATP remained unidentified for some time. In 2008, SLC17A9, the last identified member of the solute carrier 17 type I inorganic phosphate transporter family, was found to encode the vesicular nucleotide transporter (VNUT) that is responsible for the vesicular storage of ATP. VNUT transports various nucleotides in a membrane potential-dependent fashion and is expressed in the various ATP-secreting cells. Mice with knockout of the VNUT gene lose vesicular storage and release of ATP from neurons and neuroendocrine cells, resulting in blockage of the initiation of purinergic chemical transmission. Thus, VNUT plays an essential role in the vesicular storage and release of ATP. The VNUT knockout mice exhibit resistance for neuropathic pain and a therapeutic effect against diabetes by way of increased insulin sensitivity. Thus, VNUT inhibitors and suppression of VNUT gene expression may be used for therapeutic purposes through suppression of purinergic chemical transmission. This review summarizes the studies to date on VNUT and discusses what we have learned about the relevance of vesicular ATP release as a potential drug target.

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Section: Vesicular Storage Of Atpmentioning

confidence: 99%

Vesicular nucleotide transporter (VNUT): appearance of an actress on the stage of purinergic signaling

Moriyama

Hiasa

Sakamoto³

et al. 2017

Purinergic Signalling

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“…In 1997, by means of a combination of radiometric and etheno-derivative-based fluorimetric techniques, we described for the first time the transport of diadenosine polyphosphates into secretory granules, the chromaffin granules [Gualix et al, 1997].…”

Section: Diadenosine Polyphosphate Transport Into Chromaffin Granulesmentioning

confidence: 99%

“…The transport of diadenosine polyphosphates into secretory vesicles regulates the accessibility of these compounds to the extracellular space but also could be a mechanism for finishing their cytosolic actions, which would give this transport process a relevant physiological meaning. On the other hand, diadenosine pentaphosphate (Ap 5 A) transport into chromaffin granules could be inhibited by other diadenosine polyphosphates (Ap 3 A and Ap 4 A) and, to the same extent, by the non-hydrolizable analogs of ATP and ADP, ATPγS and ADPβS (Gualix et al, 1997). The inhibitory pattern of nucleotide analogs on Ap n A transport suggested that both types of substances, adenine mono-and dinucleotide, share a common vesicular transporter.…”

Section: Diadenosine Polyphosphate Transport Into Chromaffin Granulesmentioning

confidence: 99%

Nucleoside transporter and nucleotide vesicular transporter: Two examples of mnemonic regulation

Sen

Delicado

Gualix

2001

Drug Development Research

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According to their relevant roles in the regulation and availability of extracellular levels of purinergic signals, the nucleoside transporter and the nucleotide vesicular transporter are subject to acute regulation. The plasma membrane nucleoside transporter has been shown to exhibit several regulatory mechanisms, such as regulation by long-term signals, phosphorylation/dephosphorylation processes, and allosteric modulation. The present work reviews studies concerning allosteric modulation of nucleoside and nucleotide vesicular transporters, as the first reported examples of mnemonic behavior in transporter proteins, presenting kinetic and allosteric cooperativity. This fact implies that the protein can exhibit different conformations, each one with specific kinetic parameters. Transport substrates are able to induce slow conformational changes between the different forms of the transporter. This kinetic mechanism can provide several physiological advantages, since it allows strict control of transport capacity by changes in substrate concentrations. This allosteric modulation has been confirmed in several experimental models, the nucleoside transporter in chromaffin and endothelial cells from adrenal medulla and the nucleotide vesicular transporter in the chromaffin cell granules and rat brain synaptic vesicles. Taking into account these considerations, the mnemonic regulation described here could be a widespread mechanism among transporter proteins. Drug Dev. Res. 52:11-21, 2001.

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“…Vesicular uptake of these compounds is mediated through a transporter that shows a broad range of specificity, being able to internalize a large variety of mononucleotides (such ATP ADP, AMP, UTP, etc.) as well as the diadenosine polyphosphates [5,6]. All these secretory systems respond to depolarizing agents or secretagogues by releasing their vesicular content to the Electronic supplementary material The online version of this article (doi:10.1007/s11302-013-9382-3) contains supplementary material, which is available to authorized users.…”

Section: Introductionmentioning

confidence: 99%

“…extracellular medium [4,7]. In this regard, push-pull cannula experiments performed in living rats showed that after amphetamine stimulation, rat neostriatum releases diadenosine tetraphosphate, Ap 4 A, and diadenosine pentaphosphate, Ap 5 A, which can be detected in the perfusion samples at concentrations in the nanomolar range [8].…”

Section: Introductionmentioning

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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Characterization of diadenosine polyphosphate transport into chromaffin granules from adrenal medulla

Cited by 22 publications

References 1 publication

Vesicular nucleotide transporter (VNUT): appearance of an actress on the stage of purinergic signaling

Vesicular nucleotide transporter (VNUT): appearance of an actress on the stage of purinergic signaling

Nucleoside transporter and nucleotide vesicular transporter: Two examples of mnemonic regulation

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

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