Cell surface adenosine deaminase: Much more than an ectoenzyme

Franco, Rafael; Casadó, Vicent; Ciruela, Francisco; Saura, Carles; Mallol, Josefa; Lluı́s, Carmen

doi:10.1016/s0301-0082(97)00013-0

Cited by 230 publications

(176 citation statements)

References 81 publications

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“…One hypothesis would be that inosine is synthezised from adenosine taken up by neurons and released after depolarization. Alternatively, adenosine is released and converted to inosine in the extracellular medium by an ecto adenosine deaminase (Franco et al 1997). A third alternative would be the release of ATP and conversion to adenosine and inosine by ecto-nucleotidases and ecto-deaminase (Dunwiddie et al 1997, Santos et al 1999.…”

Section: -Release Experimentsmentioning

confidence: 99%

Adenosine as a signaling molecule in the retina: biochemical and developmental aspects

Paes‐de‐Carvalho¹

2002

An. Acad. Bras. Ciênc.

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The nucleoside adenosine plays an important role as a neurotransmitter or neuromodulator in the central nervous system, including the retina. In the present paper we review compelling evidence showing that adenosine is a signaling molecule in the developing retina. In the chick retina, adenosine transporters are present since early stages of development before the appearance of adenosine A1 receptors modulating dopamine-dependent adenylate cyclase activity orA2 receptors that directly activate the enzyme. Experiments using retinal cell cultures revealed that adenosine is taken up by specific cell populations that when stimulated by depolarization or neurotransmitters such as dopamine or glutamate, release the nucleoside through calciumdependent transporter-mediated mechanisms. The presence of adenosine in the extracellular medium and the long-term activation of adenosine receptors is able to regulate the survival of retinal neurons and blocks glutamate excitoxicity. Thus, adenosine besides working as a neurotransmitter or neuromodulator in the mature retina, is considered as an important signaling molecule during retinal development having important functions such as regulation of neuronal survival and differentiation.

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Section: -Release Experimentsmentioning

confidence: 99%

Adenosine as a signaling molecule in the retina: biochemical and developmental aspects

Paes‐de‐Carvalho¹

2002

An. Acad. Bras. Ciênc.

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“…Conclusion: These results suggest that the G/A genotype associated with low adenosine deaminase activity and, supposingly, with higher adenosine levels is less frequent among schizophrenic patients. 7%, p = 0,032,OR = 2,6 …”

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confidence: 99%

Lower frequency of the low activity adenosine deaminase allelic variant (ADA1*2) in schizophrenic patients

Dutra

Ottoni

Lara

et al. 2010

Rev. Bras. Psiquiatr.

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Objective: Adenosine may play a role in the pathophysiology of schizophrenia, since it modulates the release of several neurotransmitters such as glutamate, dopamine, serotonin and acetylcholine, decreases neuronal activity by pos-synaptic hyperpolarization and inhibits dopaminergic activity. Adenosine deaminase participates in purine metabolism by converting adenosine into inosine. The most frequent functional polymorphism of adenosine deaminase (22G→A) (ADA1*2) exhibits 20-30% lower enzymatic activity in individuals with the G/A genotype than individuals with the G/G genotype. The aim of this study was to evaluate the ADA polymorphism 22G→A (ADA1*2) in schizophrenic patients and healthy controls. Method: The genotypes of the ADA 22G→A were identified with allele-specific PCR strategy in 152 schizophrenic patients and 111 healthy individuals. Results: A significant decrease in the frequency of the G/A genotype was seen in schizophrenic patients (7/152 -4.6%) relative to controls (13/111 -11.7%, p = 0.032, OR = 2.6). Conclusion: These results suggest that the G/A genotype associated with low adenosine deaminase activity and, supposingly, with higher adenosine levels is less frequent among schizophrenic patients. 7%, p = 0,032,OR = 2,6 Descriptors

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“…Ecto-adenosine deaminase (ecto-ADA; EC 3.5.4.4), which is capable of degrading adenosine to inosine on the cell surface (for a review, see Ref. 33), was shown to modulate ligand binding and signaling through A 1 Rs on DDT 1 MF-2 cells (34). Irrespective of its catalytic activity, ADA seems to be necessary for a high affinity binding of agonists to A 1 R (35).…”

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confidence: 99%

Adenosine Deaminase and A1 Adenosine Receptors Internalize Together following Agonist-induced Receptor Desensitization

Saura

Mallol

Canela

et al. 1998

Journal of Biological Chemistry

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Adenosine is an autacoid that exerts its physiological actions through specific cell surface receptors. Four adenosine receptors (A 1 , A 2A , A 2B , and A 3 ), belonging to the family of G protein-coupled receptors, have been cloned and pharmacologically characterized (1). Acting through different adenosine receptors, adenosine is a neuromodulator in both the central and peripheral nervous systems (2, 3). Via A 1 adenosine receptors (A 1 Rs), 1 adenosine reduces heart rate (4), glomerular filtration rate, and renin release in the kidney (5); it induces bronchoconstriction (6, 7) and inhibits lipolysis. A 1 Rs can be coupled to different pertussis toxin-sensitive G proteins (8 -10), which mediate inhibition of adenylate cyclase (11) and regulate Ca 2ϩ and K ϩ channels and inositol phosphate metabolism (1). A 1 R displays two different affinities for agonist, which have classically been attributed to a different coupling to heterotrimeric G proteins (12). According to this two-independent site model, coupled receptor-G protein complexes display high affinity for agonists (K d ϭ 0.1-0.2 nM), and uncoupled receptors display low affinity (1-2 nM) (12, 13). The recently reported cluster-arranged cooperative model predicts that the high and low affinity sites are a consequence of the negative cooperativity of agonist binding and do not seem to be related to the content of free and G protein-coupled receptors (14). According to the cluster-arranged cooperative model, the agonist-induced conversion of the high to the low affinity state may partially explain the ligand-induced desensitization of A 1 R (14, 15).Receptors belonging to the G protein-coupled receptor family are desensitized and down-regulated in response to agonist stimulation. ␤ 2 -Adrenergic receptors (␤ 2 -ARs) constitute the best characterized system within the G protein-coupled receptor family. Agonist-induced ␤ 2 -AR desensitization is caused by a conformational change of the agonist-occupied receptor that facilitates receptor phosphorylation by second messenger-activated kinases or G protein-coupled receptor kinases (16,17). Following ␤ 2 -AR phosphorylation, ␤-arrestin binds to the phosphorylated receptor and uncouples the receptor from the heterotrimeric G proteins (18,19). ␤-Arrestin not only desensitizes the receptor but also functions as a clathrin adaptor, mediating receptor sequestration, i.e. receptor internalization toward intracellular compartments (20,21). Although sequestration is not required for phosphorylation and desensitization, it appears to be necessary for dephosphorylation and resensitization of ␤ 2 -ARs (22, 23).Like other G protein-coupled receptor members, A 1 R expression is regulated in response to agonist or antagonist stimulation. Desensitization of A 1 R has been described in intact animals and in cell cultures. Prolonged administration of A 1 R agonists to animals leads to functional desensitization of A 1 R in guinea pig heart (24), rat adipocytes (25), rat atrial muscle (26), and rat brain (27,28). The reduced functiona...

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Cell surface adenosine deaminase: Much more than an ectoenzyme

Cited by 230 publications

References 81 publications

Adenosine as a signaling molecule in the retina: biochemical and developmental aspects

Adenosine as a signaling molecule in the retina: biochemical and developmental aspects

Lower frequency of the low activity adenosine deaminase allelic variant (ADA1*2) in schizophrenic patients

Adenosine Deaminase and A1 Adenosine Receptors Internalize Together following Agonist-induced Receptor Desensitization

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