Chapter 15 Adenine nucleotides as inhibitors of synaptic transmission: Role of localised ectonucleotidases

Am, Sebastião; Ra, Cunha; Jf, Cascalheira; Ja, Ribeiro

doi:10.1016/s0079-6123(08)63555-4

Cited by 21 publications

(20 citation statements)

References 55 publications

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“…In agreement with this idea, Dunwiddie et al (1997) and Cunha et al (1998) demonstrated that in the rat hippocampus, extracellular ATP and adenine nucleotides are rapidly and locally hydrolyzed to Ade by ectonucleotidases, thereby inducing a response through the activation of P 1 Ade receptors. The responses described for the rat hippocampus showed agonist selectivity that was very similar to those reported for peripheral tissues, but they exhibited a significant decline in the presence of ADA and a marked enhancement in the presence of Ade uptake inhibitors (Cunha et al, 1998;Sebastiã o et al, 1999), which is somewhat inconsistent with the existence of a novel purinoceptor.…”

supporting

confidence: 60%

“…In contrast, Sebastiã o et al (1999) suggested that presynaptic inhibition of neurotransmitter release by adenine nucleotides is mediated by Ade, which is produced by the ectonucleotidase cascade. In agreement with this idea, Dunwiddie et al (1997) and Cunha et al (1998) demonstrated that in the rat hippocampus, extracellular ATP and adenine nucleotides are rapidly and locally hydrolyzed to Ade by ectonucleotidases, thereby inducing a response through the activation of P 1 Ade receptors.…”

mentioning

confidence: 99%

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Adenine Nucleotide-Induced Activation of Adenosine A_2BReceptors Expressed inXenopus laevisOocytes: Involvement of a Rapid and Localized Adenosine Formation by Ectonucleotidases

Matsuoka

Ohkubo²,

Kimura³

et al. 2002

Mol Pharmacol

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We recently demonstrated that extracellular ATP effectively activates adenosine (Ade) A 2B receptors indirectly through a localized rapid conversion to Ade by ectonucleotidases on the membrane surface of C6Bu-1 rat glioma cells. These responses were observed even in the presence of adenosine deaminase (ADA). Here, we demonstrate that such responses indeed occur in A 2B receptor-expressing Xenopus laevis oocytes, which possess endogenous ectonucleotidase activity. In oocytes coexpressing the A 2B receptor and cystic fibrosis transmembrane conductance regulator (CFTR), Ade induced a concentrationdependent increase in a cyclic AMP-activated CFTR current, a response that was inhibited by the P1 antagonist xanthineamine congener (XAC). A brief application of ATP and ␤,␥-methylene ATP (␤,␥-MeATP) also induced the CFTR current in a manner similar to that seen with Ade. Among several nucleotide agonists, ADP, AMP, and adenosine-5Ј-O-(3-thio)triphosphate induced the CFTR current. Although adenine nucleotideinduced CFTR currents were inhibited by XAC, they were highly resistant to ADA treatment; 5 U/ml ADA was required for inhibition of adenine nucleotide-induced CFTR current, whereas 1 U/ml ADA was sufficient to abolish the Ade-induced response. In addition, the ecto-5Ј-nucleotidase inhibitor ␣,␤-methylene ADP markedly inhibited the ␤,␥-MeATP-induced response but not the Ade-induced one. These results support our hypothesis that adenine nucleotides are rapidly and locally converted into Ade on the membrane surface, resulting in the activation of A 2B

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supporting

confidence: 60%

mentioning

confidence: 99%

Adenine Nucleotide-Induced Activation of Adenosine A_2BReceptors Expressed inXenopus laevisOocytes: Involvement of a Rapid and Localized Adenosine Formation by Ectonucleotidases

Matsuoka

Ohkubo²,

Kimura³

et al. 2002

Mol Pharmacol

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“…This demands the use of appropriate models to study presynaptic function, like the synaptosomes [144], although modulation through action potential propagation cannot be recorded, or neurite preparations [52,151], which cannot ascribe an effect to nerve terminals. It will also be necessary to exclude adenosine (A 1 , A 2A and the still ill-defined A 3 ) receptor involvement [29], and to use biochemical analysis to support a presynaptic localisation of P2 receptors using radioligands [e.g. 88] and immunological approaches [79][80][81][82][83][84][85][86], mainly using electron microscopy immunocytochemistry [82,84,86].…”

Section: Discussionmentioning

confidence: 99%

“…the ability of ATP-derived adenosine to activate A 1 receptors without equilibrating with the biophase [26][27][28], makes it mandatory to appropriately exclude the involvement of adenosine A 1 receptors in any presynaptic inhibitory effect of ATP [reviewed in 29,30]. The existence of this channelling process probably accounts for the proposed direct action of adenine nucleotides on adenosine A 1 receptors (27)(28)(29)(30)(31). Facilitatory effects of ATP may also be confounded by facilitatory effects of adenosine via activation of adenosine A 2A receptors [36,37].…”

Section: Problems Found In Defining and Classifying Atp-mediated Presmentioning

confidence: 99%

ATP as a presynaptic modulator

2000

Self Cite

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There is considerable evidence that ATP acts as a fast transmitter or co-transmitter in autonomic and sensory nerves mostly through activation of ionotropic P2X receptors but also through metabotropic P2Y receptors. By analogy, the observations that ATP is released from stimulated central nervous system (CNS) nerve terminals and that responses to exogenously added ATP can be recorded in central neurons, lead to the proposal that ATP might also be a fast transmitter in the CNS. However, in spite of the robust expression of P2 receptor mRNA and binding to P2 receptors in the CNS, the demonstration of central purinergic transmission has mostly remained elusive. We now review evidence to suggest that ATP may also act presynaptically rather than solely postsynaptically in the nervous system.

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“…Critical role of local adenosine formation in the ATP-induced response has been suggested in the rat hippocampus (23,24) and frog neuromuscular junction (25). In those studies, ATP was supposed to undergo rapid hydrolysis to adenosine within <1 s and subsequently inhibit neurotransmission via the A 1 receptor.…”

Section: Rapid and Localized Adenosine Generation On Membrane Surfacementioning

confidence: 99%

ATP- and Adenosine-Mediated Signaling in the Central Nervous System: Adenosine Receptor Activation by ATP Through Rapid and Localized Generation of Adenosine by Ecto-nucleotidases

Matsuoka

Ohkubo

2004

J Pharmacol Sci

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Abstract. Extracellular ATP is now recognized as a neurotransmitter or neuromodilator in the nervous system, producing diverse physiological effects by activating multiple P2 receptors. Although P2-receptor signaling is terminated by hydrolysis of ATP by the ecto-nucleotidase cascade, such a metabolic step leads to adenosine generation, thereby initiating adenosine (P1)-receptor activation. Because most cells and tissues co-express P1 and P2 receptors, ecto-nucleotidase on target tissues, especially enzymes catalyzing adenosine formation, are determinants of the cellular response to ATP. Ecto-5'-nucleotidase (E-5'-NT) has been considered to play a principal role in conversion of AMP to adenosine. In addition to E-5'-NT, we have recently demonstrated that ecto-alkaline phosphatase is also involved in ATP-induced P1-receptor activation through a rapid and localized adenosine production on the membrane surface. In this minireview, we describe the pharmacological profile of ecto-nucleotidase-dependent P1-receptor activation by ATP and molecular bases of preferential delivery of metabolically generated adenosine to P1 receptors. Several lines of evidence suggest that the close association between ecto-nucleotidases and P1 receptors may constitute a functional receptor for extracellular ATP, and some physiological responses to ATP would occur through this mechanism.

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Chapter 15 Adenine nucleotides as inhibitors of synaptic transmission: Role of localised ectonucleotidases

Cited by 21 publications

References 55 publications

Adenine Nucleotide-Induced Activation of Adenosine A_2BReceptors Expressed inXenopus laevisOocytes: Involvement of a Rapid and Localized Adenosine Formation by Ectonucleotidases

Adenine Nucleotide-Induced Activation of Adenosine A_2BReceptors Expressed inXenopus laevisOocytes: Involvement of a Rapid and Localized Adenosine Formation by Ectonucleotidases

ATP as a presynaptic modulator

ATP- and Adenosine-Mediated Signaling in the Central Nervous System: Adenosine Receptor Activation by ATP Through Rapid and Localized Generation of Adenosine by Ecto-nucleotidases

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Chapter 15 Adenine nucleotides as inhibitors of synaptic transmission: Role of localised ectonucleotidases

Cited by 21 publications

References 55 publications

Adenine Nucleotide-Induced Activation of Adenosine A2BReceptors Expressed inXenopus laevisOocytes: Involvement of a Rapid and Localized Adenosine Formation by Ectonucleotidases

Adenine Nucleotide-Induced Activation of Adenosine A2BReceptors Expressed inXenopus laevisOocytes: Involvement of a Rapid and Localized Adenosine Formation by Ectonucleotidases

ATP as a presynaptic modulator

ATP- and Adenosine-Mediated Signaling in the Central Nervous System: Adenosine Receptor Activation by ATP Through Rapid and Localized Generation of Adenosine by Ecto-nucleotidases

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Resources

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Adenine Nucleotide-Induced Activation of Adenosine A_2BReceptors Expressed inXenopus laevisOocytes: Involvement of a Rapid and Localized Adenosine Formation by Ectonucleotidases

Adenine Nucleotide-Induced Activation of Adenosine A_2BReceptors Expressed inXenopus laevisOocytes: Involvement of a Rapid and Localized Adenosine Formation by Ectonucleotidases