Zaprinast stimulates extracellular adenosine accumulation in rat pontine slices

Le, Minou; Lu, Yin; Li, Ya; Greene, Robert; Epstein, Paul M.; Rosenberg, Paul A.

doi:10.1016/j.neulet.2004.07.090

Cited by 4 publications

(4 citation statements)

References 36 publications

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“…To investigate whether the extracellular adenosine accumulation could be derived from extracellular ATP or cAMP transported out of the cell we used the membrane‐impermeable inhibitor of 5′‐nucleotidase AMP‐CP (Pearson, 1987; Le et al ., 2004) to block the last step leading to the production of extracellular adenosine from the hydrolysis of 5′‐AMP. Application of AMP‐CP (100 µ m ) did not alter the response to DEA/NO (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Zaprinast is a PDE inhibitor that induces release of adenosine in several neuronal preparations (Broome et al ., 1994; Le et al ., 2004; Lu et al ., 2004), and this effect of zaprinast has been used as evidence for involvement of cGMP in the regulation of extracellular adenosine levels by nitric oxide (Boulton et al ., 1994; Saransaari & Oja, 2004). We found that zaprinast (5 µ m ) depressed the CA1 fEPSP slope by 47.9 ± 4.2% ( n = 9; Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In neuronal cultures we found that zaprinast‐evoked adenosine accumulation was mediated by an increase in glutamate release and the activation of NMDA receptors (Lu et al ., 2004). However, in hippocampal slices, as in pontine slices (Le et al ., 2004), zaprinast‐stimulated adenosine accumulation was not blocked by NMDA receptor antagonists.…”

Section: Discussionmentioning

confidence: 98%

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Nitric oxide‐induced adenosine inhibition of hippocampal synaptic transmission depends on adenosine kinase inhibition and is cyclic GMP independent

Arrigoni

Rosenberg

2006

Eur J of Neuroscience

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Adenosine is an important inhibitory neuromodulator that regulates neuronal excitability. Several studies have shown that nitric oxide induces release of adenosine. Here we investigated the mechanism of this release. We studied the effects of nitric oxide on evoked field excitatory postsynaptic potentials (fEPSPs) recorded in the CA1 area of rat hippocampal slices. The nitric oxide donor 1,1-diethyl-2-hydroxy-2-nitroso-hydrazine sodium (DEA/NO; 100 microm) depressed the fEPSP by 77.6 +/- 4.1%. This effect was abolished by the adenosine A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 400 nm), indicating that the nitric oxide effect was mediated by adenosine accumulation. The DEA/NO effect was unaltered by the 5'-ectonucleotidase inhibitor alpha,beta-methylene-adenosine 5'-diphosphate (AMP-CP; 100 microm), indicating that extracellular adenosine did not derive from ATP or cAMP release. The guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazole[4,3-a]quinoxaline-1-one (ODQ; 5 microm) did not affect nitric oxide depression of the fEPSPs, indicating that nitric oxide-mediated adenosine release was not mediated through a cGMP signaling cascade. This conclusion was confirmed by the observation that 8-(4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP; 1 mm) reversibly depressed the fEPSP by 24.9 +/- 4.5%, but this effect was not blocked by adenosine antagonists. Adenosine kinase inhibitor 5-iodotubercidin (ITU; 7 microm) occluded the nitric oxide effects by 74%, suggesting that inhibition of adenosine kinase activity contributes to adenosine release. In conclusion, exogenous nitric oxide evokes adenosine release by a cGMP-independent pathway. Intracellular cGMP elevation partially inhibits the fEPSP but not through adenosine release. Although a direct block of adenosine kinase by nitric oxide can not be excluded, the depression of adenosine kinase activity may be due to inhibition by its own substrate adenosine.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 98%

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Nitric oxide‐induced adenosine inhibition of hippocampal synaptic transmission depends on adenosine kinase inhibition and is cyclic GMP independent

Arrigoni

Rosenberg

2006

Eur J of Neuroscience

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“…[19][20][21][22][23] Moreover, it has been demonstrated that primary human dermal fibroblasts and other fibroblasts release increasing amounts of adenosine under stimulated conditions, such as after exposure to H 2 O 2 , stimulated polymorphonuclear neutrophils, or mechanic load treatment. [24][25][26] This occurs, in part, as an adaptive mechanism; it has been demonstrated previously that adenosine receptor occupancy suppresses the generation of reactive oxygen species by stimulated neutrophils and other cells. [27][28][29][30] However, when the oxidative insult results from nonsuppressible causes, such as a toxin or an ongoing immunologic reaction, release of adenosine may be maladaptive and can promote scarring, as shown herein.…”

Section: Discussionmentioning

confidence: 99%

Absence of the Adenosine A2A Receptor Attenuates Hypertrophic Scarring in Mice

Huo

Wang

et al. 2013

Journal of Burn Care & Research

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Hypertrophic scar following cutaneous wounding is the result of the body overproducing collagen, and it has been shown that the activation of the adenosine A(2A) receptor promotes tissue repair, wound healing, and extracellular matrix production. In this study, we explored the role of adenosine receptor in hypertrophic scarring in adenosine A(2A) receptor knockout mice models. Mechanical stress was applied to a healing wound to produce hypertrophic scars in adenosine A(2A) receptor knockout mice and wild-type controls. Total scar areas were evaluated after routine hematoxylin and eosin and picrosirius red staining and hydroxyproline content measured colorimetrically. Expression of transforming growth factor-β in scar tissues was measured using the Western blotting method. Compared with the wild-type control group, adenosine A(2A) receptor knockout mice showed significantly less thickness, smaller cross-sectional area, and significantly lower hydroxyproline levels and transforming growth factor-β levels. These results demonstrate that adenosine A(2A) receptors play an active role in the pathogenesis of dermal fibrosis and suggest a novel therapeutic target in the prevention and treatment of hypertrophic scarring.

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Regulation of long-term depression by increases in [guanosine 3′,5′-cyclic monophosphate] in the hippocampal CA1 region of freely behaving rats

Stricker

Manahan‐Vaughan

2009

Neuroscience

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Zaprinast stimulates extracellular adenosine accumulation in rat pontine slices

Cited by 4 publications

References 36 publications

Nitric oxide‐induced adenosine inhibition of hippocampal synaptic transmission depends on adenosine kinase inhibition and is cyclic GMP independent

Nitric oxide‐induced adenosine inhibition of hippocampal synaptic transmission depends on adenosine kinase inhibition and is cyclic GMP independent

Absence of the Adenosine A2A Receptor Attenuates Hypertrophic Scarring in Mice

Regulation of long-term depression by increases in [guanosine 3′,5′-cyclic monophosphate] in the hippocampal CA1 region of freely behaving rats

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