Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In cultured striatal astrocytes, 2-chloroadenosine, an adenosine analog resistant to adenosine deaminase, although inactive alone, markedly potentiated the activation of phospholipase C induced by methoxamine, an alpha 1-adrenergic agonist. This effect was suppressed by antagonists of either A1 adenosine or alpha 1-adrenergic receptors. An influx of calcium and two distinct G-proteins are involved in this phenomenon since the potentiating effect of 2-chloradenosine was suppressed in the absence of external calcium or when cells were pretreated with pertussis toxin. In addition, arachidonic acid is likely involved in this potentiating effect. This was shown first by examining the effects of inhibitors of phospholipase A2 or arachidonic metabolism, then by examining the action of arachidonic acid on the production of inositol phosphates in either the presence or absence of methoxamine, and finally by measuring the release of arachidonic acid. The sequential activation of phospholipase C and of protein kinase C is required for the 2-chloroadenosine-induced activation of phospholipase A2 since 2-chloroadenosine markedly stimulated phospholipase C activity in the absence of methoxamine when protein kinase C was activated by a diacylglycerol analog. Finally, the enhancing effect of 2-chloroadenosine on the methoxamine-evoked response seems to result from an inhibition of glutamate reuptake into astrocytes by arachidonic acid. Indeed, the potentiating effect of 2-chloroadenosine was suppressed when external glutamate was removed enzymatically and mimicked by either selective inhibitors of the glutamate reuptake process or direct application of glutamate.
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PMID:2-Chloroadenosine potentiates the alpha 1-adrenergic activation of phospholipase C through a mechanism involving arachidonic acid and glutamate in striatal astrocytes. 134 73

Purine release and prostaglandin (PG) outflow were simultaneously evaluated from untreated glial primary cultures of rat striatum, at rest and under field electrical stimulation. Purine release was also assayed from sister cultured cells in which a suitable pharmacological treatment with 1 x 10(-6) M dexamethasone or 1 x 10(-4) M indomethacin had produced a complete inhibition of the phospholipase A2-prostaglandin (PLA2-PG) system. Purine release from untreated cells seems to be regulated by specific receptor sites for released adenosine (Ado); A1 receptors exert an inhibitory control on purine release while A2 receptors facilitate it. PG release appears to be related to A1-mediated Ado activity, since culture treatment with 1 x 10(-10) M 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or 1 x 10(-4) M N-ethylmaleimide (NEM), A1 receptor inhibitory agents able to increase purine release, induced a significant reduction of the evoked PG outflow. Purine amount, released from glial cells with inhibited PLA2-PG system, was remarkably greater than that one assayed from control cultured cells. In so treated cultures, no additive effect, NEM-induced, was detected, while the addition of a mixture of PGs partially reduced the increased purine outflow. An electrically evoked cAMP accumulation, significantly greater than that found in controls, was even detected in cultured cells with inhibited PLA2-PG system. Since 10 micrograms/ml adenosine deaminase (ADA) reduced while DPCPX enhanced the evoked cAMP accumulation, it seems partially due to released Ado and accounts for a prevalent A2-stimulating rather than an A1-inhibitory control on adenylate cyclase activity. Thus, in cultured glial cells, the PLA2-PG system, likely linked to A1 receptor sites, concurs to control purine release and seems to affect less directly cAMP accumulation.
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PMID:Influence of PLA2-PG system on purine release and cAMP content in dissociated primary glial cultures from rat striatum. 254 40

Exposure of brown adipocytes to phenylephrine activates a phospholipase A2 producing arachidonic acid and lysophospholipids. When adipocytes were incubated with adenosine deaminase, a greater release of arachidonic acid and accumulation of lysophosphatidyl-choline in response to phenylephrine was noted. The potentiating effect of adenosine deaminase was also observed in the presence of A23187 and for both stimuli, the effect of adenosine deaminase was reversed by phenylisopropyladenosine. These results suggest the presence of an heretofore unrecognized action of adenosine, namely inhibition of phospholipase A2 activity in brown fat cells.
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PMID:Adenosine inhibits phenylephrine activation of phospholipase A in hamster brown adipocytes. 313 56

As shown on cultured astrocytes from the mouse, in the presence of adenosine deaminase, 2-chloroadenosine by acting on A1-adenosine receptors potentiated the activation of phospholipase C induced by the alpha 1-adrenergic agonist, methoxamine. This potentiation required the presence of external calcium and was blocked by pertussis toxin. Moreover, this potentiation resulted from a cascade of events: activation (by calcium and protein kinase C) of a phospholipase A2 coupled to A1-adenosine receptors, release of arachidonic acid, which inhibited the reuptake of glutamate into astrocytes and finally additional activation of phospholipase C by externally accumulated glutamate through metabotropic receptors. The effects of 2-chloroadenosine and methoxamine were respectively mimicked by somatostatin and substance P while endothelins reproduced the combined effects of 2-chloroadenosine and methoxamine. Conditioned media from treated astrocytes enriched in glutamate stimulated phospholipase C in cultured striatal neurones. In addition, glutamate alone was also found to stimulate phospholipase A2 in astrocytes through receptors exhibiting a pharmacological profile distinct from metabotropic receptors coupled to phospholipase C and the glutamate response was potentiated by ATP. Moreover, the neuronal arachidonic acid production evoked by glutamate was potentiated by acetylcholine. Finally, the combined application of 2-chloroadenosine and methoxamine on striatal astrocytes reduced the permeability of gap junctions between astrocytes and this response was mimicked by arachidonic acid. Together, these results emphasized the contribution of astrocytes in the regulation of glutamatergic transmission.
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PMID:Glial receptors and their intervention in astrocyto-astrocytic and astrocyto-neuronal interactions. 792 48

1. In rat mesangial cells extracellular nucleotides were found to increase arachidonic acid release by a cytosolic phospholipase A(2) through the P2Y(2) purinergic receptor. 2. In this study we investigated the effects of ATP and UTP on interleukin-1ss (IL-1ss)-induced mRNA expression and activity of group IIA phospholipase A(2) (sPLA(2)-IIA) in rat mesangial cells. 3. Treatment of cells for 24 h with extracellular ATP potentiated IL-1ss-stimulated sPLA(2)-IIA induction, whereas UTP had no effect. 4. We obtained the following evidence that the P2Y(2) receptor is not involved in the potentiation of sPLA(2)-IIA induction: (i) ATP-gamma-S had no enhancing effect; (ii) suramin, a P(2) receptor antagonist, did not inhibit ATP-mediated potentiation; (iii) inhibition of degradation of extracellular nucleotides by the 5'-ectonucleotidase inhibitor AOPCP did not enhance sPLA(2)-IIA induction and (iv) adenosine deaminase treatment completely abolished the ATP-mediated potentiation of sPLA(2)-IIA induction. 5. In contrast, treatment of mesangial cells with adenosine or the A2A receptor agonist CGS 21680 mimicked the effects of ATP in enhancing IL-1ss-stimulated sPLA(2)-IIA induction, whereas the specific A2A receptor antagonist ZM 241385 completely abolished the potentiating effect of ATP or adenosine. 6. The protein kinase A inhibitor Rp-8-Br-cyclic AMPS dose-dependently inhibited the enhancing effect of ATP or adenosine indicating the participation of an adenosine receptor-mediated cyclic AMP-dependent signalling pathway. 7. These data indicate that ATP mediates proinflammatory long-term effects in rat mesangial cells via its degradation product adenosine through the A2A receptor resulting in potentiation of sPLA(2)-IIA induction.
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PMID:Potentiation of cytokine induction of group IIA phospholipase A(2) in rat mesangial cells by ATP and adenosine via the A2A adenosine receptor. 1115 59

Neutrophils are physiologically associated with platelets in whole blood. Inflammatory reactions can be modulated by the presence of platelets. To investigate the influence of platelets on neutrophil activity, we studied the 5-lipoxygenase (5-LOX) metabolic pathway in normal human blood neutrophils stimulated with f-Met-Leu-Phe (fMLP) or monosodium urate monohydrate (MSUM) in the presence of autologous platelets. Platelets inhibited by more than 90% the synthesis of leukotriene B(4) and 5-HETE in neutrophils activated with fMLP or MSUM. The addition of exogenous arachidonic acid did not reverse the inhibitory effect of platelets on 5-LOX-generated metabolites in fMLP- or MSUM-activated neutrophils. Preincubation of neutrophils with adenosine deaminase reversed the inhibitory effect of platelets in fMLP-treated neutrophils, indicating that adenosine was responsible for the platelet inhibition of leukotriene B(4) and 5-HETE formation. In contrast, adenosine deaminase had no influence on the inhibitory effects of platelets in MSUM-stimulated cells. These results suggest that platelets can inhibit the synthesis of 5-LOX products (a). by acting mainly downstream to phospholipase A(2) in cells stimulated by fMLP or MSUM, (b). through adenosine when neutrophils are activated with fMLP, and (c). by an adenosine-independent mechanism in MSUM-activated neutrophils by an as-yet-unidentified mediator.
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PMID:Platelets abrogate leukotriene B(4) generation by human blood neutrophils stimulated with monosodium urate monohydrate or f-Met-Leu-Phe in vitro. 1269 52