Adenosine deaminase: Functional implications and different classes of inhibitors

Cristalli, Gloria; Costanzi, Stefano; Lambertucci, Catia; Lupidi, Giulio; Vittori, Sauro; Volpini, Rosaria; Camaioni, Emidio

doi:10.1002/1098-1128(200103)21:2<105::aid-med1002>3.0.co;2-u

Cited by 289 publications

(271 citation statements)

References 199 publications

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“…Coperfusion of an adenosine-specific deaminase (Cristalli et al, 2001) reversed the outward current caused by BzATP (Fig. 3).…”

Section: Bzatp Is Converted To Adenosine By a Combined Action Of Ectomentioning

confidence: 85%

“…A similar outward current was recorded when 65 M adenosine was added after preapplication of a high adenosine concentration (300 -600 M; 4.9 Ϯ 0.4 pA; n ϭ 4; data not shown). Moreover, coperfusion of slices with adenosine deaminase (2 U/ml), an enzyme that converts adenosine (and 2Ј-deoxyadenosine) to its inactive metabolite inosine (and 2Ј-deoxyinosine) (Cristalli et al, 2001), resulted in a complete reversal of the current evoked either by BzATP or by adenosine (Fig. 3C).…”

Section: Bzatp Leads To Activation Of An a 1 Receptor-coupled Potassimentioning

confidence: 96%

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Ecto-Nucleotidases and Nucleoside Transporters Mediate Activation of Adenosine Receptors on Hippocampal Mossy Fibers by P2X₇Receptor Agonist 2′-3′-O-(4-Benzoylbenzoyl)-ATP

Kukley

Stausberg²,

Adelmann³

et al. 2004

J. Neurosci.

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The ionotropic and cytolytic P2X 7 receptor is typically found on immune cells, where it is involved in the release of cytokines. Recently, P2X 7 receptors were reported to be localized to presynaptic nerve terminals and to modulate transmitter release. In the present study, we reassessed this unexpected role of P2X 7 receptors at hippocampal mossy fiber-CA3 synapses. In agreement with previous findings, the widely used P2X 7 agonist 2Ј-3Ј-O-(4-benzoylbenzoyl)-adenosine-5Ј-triphosphate (BzATP) clearly depressed field potentials (fEPSPs); however, no evidence for an involvement of P2X 7 receptors could be obtained. First, depression of fEPSPs by BzATP was unchanged in P2X 7 Ϫ/Ϫ mice. Second, experiments using P2X 7 Ϫ/Ϫ mice, immunohistochemistry, and electron microscopy showed that the antigen detected by frequently used P2X 7 antibodies is not compatible with a plasmalemmal P2X 7 receptor. Third, BzATP did not alter Ca 2ϩ levels in synaptic terminals. In contrast, the depression of fEPSPs by BzATP was fully blocked by adenosine (A 1 ) receptor antagonists. Furthermore, the application of BzATP also activated postsynaptic A 1 receptor-coupled K ϩ channels. This effect of BzATP was mimicked by ATP and adenosine and was completely prevented by enzymes specifically degrading adenosine. Activation of A 1 -coupled K ϩ channels by BzATP was dependent on ecto-nucleotidases, extracellular enzymes that convert ATP to adenosine. Moreover, the opening of A 1 -coupled K ϩ channels by BzATP was dependent on nucleoside transporters. Taken together, our results indicate that BzATP is extracellularly catabolized to Bz-adenosine and subsequently hetero-exchanged for intracellular adenosine and then depresses mossy fiber fEPSPs through presynaptic A 1 receptors rather than through P2X 7 receptors. Thus, the present study casts doubts on the neuronal localization of P2X 7 receptors in rodent hippocampus.

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“…Coperfusion of an adenosine-specific deaminase (Cristalli et al, 2001) reversed the outward current caused by BzATP (Fig. 3).…”

Section: Bzatp Is Converted To Adenosine By a Combined Action Of Ectomentioning

confidence: 85%

Section: Bzatp Leads To Activation Of An a 1 Receptor-coupled Potassimentioning

confidence: 96%

Ecto-Nucleotidases and Nucleoside Transporters Mediate Activation of Adenosine Receptors on Hippocampal Mossy Fibers by P2X₇Receptor Agonist 2′-3′-O-(4-Benzoylbenzoyl)-ATP

Kukley

Stausberg²,

Adelmann³

et al. 2004

J. Neurosci.

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“…The set of KIEs for the three ADAs were determined under competitive conditions. The intrinsic [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] N], [6-13 C], and [6- 30 Adenylate kinase (AK), pyruvate kinase (PK), hexokinase, and bovine spleen adenosine deaminase (BtADA) were purchased from Sigma. Phospho-D-ribosyl-1-pyrophosphate (PRPP) synthase and adenine phosphoribosyltransferase (APRTase) were purified according to the methods reported previously.…”

Section: Introductionmentioning

confidence: 99%

Transition-State Variation in Human, Bovine, and Plasmodium falciparum Adenosine Deaminases

2007

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Adenosine deaminases (ADAs) from human, bovine and Plasmodium falciparum sources were analyzed by kinetic isotope effects (KIEs) and shown to have distinct but related transition states. Human adenosine deaminase (HsADA) is present in most mammalian cells and is involved in Band T-cell development. The ADA from Plasmodium falciparum (PfADA) is essential in this purine auxotroph and its inhibition is expected to have therapeutic effects for malaria. Therefore ADA is of continuing interest for inhibitor design. where N1 protonation is partial and the bond order to the attacking hydroxyl nucleophile is nearly complete. The key structural variation among PfADA, HsADA and BtADA transition states lies in the degree of N1 protonation with the decreased bond lengths of 1.92 Å, 1.55 Å and 1.28 Å, respectively. Thus, PfADA has the earliest and BtADA has most developed transition state. This conclusion is consistent with the 20 to 36-fold increase of k cat in comparing PfADA with HsADA and BtADA.

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“…This explains why ADA activity can be high in acute effusions, including that one in which cellular differentiation pattern is predominantly neutrophilic 22 . It is important to remember that ADA is present in all mammalian cells and, despite a number of studies performed to date, the physiological role that it plays in the different tissues is not yet clear 8 .…”

Section: Introductionmentioning

confidence: 99%

The usefulness of adenosine deaminase in the diagnosis of tuberculous pericarditis

Tuon

Silva

Almeida

et al. 2007

Rev. Inst. Med. trop. S. Paulo

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SUMMARYThe objective of this study was to evaluate the adenosine deaminase (ADA) activity usefulness in the diagnosis of tuberculous pericarditis (TP), comparing its value with pericardial effusions (PE) caused by other pericardial diseases. A retrospective casecontrol study was conducted with nine cases of TP and 39 other than TP diseases (12 neoplastic, 11 septic and 16 unknown origin). Every patient included in this study had PE samples submitted to ADA activity measures and microbiological analysis, and then had pericardial tissue samples submitted to microbiological and histopathological examination. Considering the value of 40 U/L as the cut-off for the diagnosis of TP, the specificity and sensitivity were respectively of 72% and 89%. The specificity of ADA activity for the TP was best applied in the differential diagnosis from PE of unknown origin. The present study demonstrates the clinical value of the measurement of ADA activity in PE in the diagnosis of TP.

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Adenosine deaminase: Functional implications and different classes of inhibitors

Cited by 289 publications

References 199 publications

Ecto-Nucleotidases and Nucleoside Transporters Mediate Activation of Adenosine Receptors on Hippocampal Mossy Fibers by P2X₇Receptor Agonist 2′-3′-O-(4-Benzoylbenzoyl)-ATP

Ecto-Nucleotidases and Nucleoside Transporters Mediate Activation of Adenosine Receptors on Hippocampal Mossy Fibers by P2X₇Receptor Agonist 2′-3′-O-(4-Benzoylbenzoyl)-ATP

Transition-State Variation in Human, Bovine, and Plasmodium falciparum Adenosine Deaminases

The usefulness of adenosine deaminase in the diagnosis of tuberculous pericarditis

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Adenosine deaminase: Functional implications and different classes of inhibitors

Cited by 289 publications

References 199 publications

Ecto-Nucleotidases and Nucleoside Transporters Mediate Activation of Adenosine Receptors on Hippocampal Mossy Fibers by P2X7Receptor Agonist 2′-3′-O-(4-Benzoylbenzoyl)-ATP

Ecto-Nucleotidases and Nucleoside Transporters Mediate Activation of Adenosine Receptors on Hippocampal Mossy Fibers by P2X7Receptor Agonist 2′-3′-O-(4-Benzoylbenzoyl)-ATP

Transition-State Variation in Human, Bovine, and Plasmodium falciparum Adenosine Deaminases

The usefulness of adenosine deaminase in the diagnosis of tuberculous pericarditis

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Ecto-Nucleotidases and Nucleoside Transporters Mediate Activation of Adenosine Receptors on Hippocampal Mossy Fibers by P2X₇Receptor Agonist 2′-3′-O-(4-Benzoylbenzoyl)-ATP

Ecto-Nucleotidases and Nucleoside Transporters Mediate Activation of Adenosine Receptors on Hippocampal Mossy Fibers by P2X₇Receptor Agonist 2′-3′-O-(4-Benzoylbenzoyl)-ATP