Different modulation of inhibitory and stimulatory pathways mediated by adenosine after chronic in vivo agonist exposure

Ruiz, María Ángeles; Albasanz, José Luís; León, David; Ros, Manuel; Andrés, Antonio; Martı́n, Mairena

doi:10.1016/j.brainres.2004.10.040

Cited by 10 publications

(10 citation statements)

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“…Conceivably, prolonged systemic exposure to LPS could downregulate expression of adenosine A 1 receptors and/or downstream intracellular signaling cascade(s) in cheek pouch microcirculation either directly or through elaboration of cytokines and chemokines [4, 6–8, 17–24]. To this end, Ruiz and her colleagues [18] and León et al [19] showed that prolonged exposure to selective adenosine A 1 receptor agonists, such as R(−)-PIA, decreases significantly the number of high-affinity adenosine A 1 receptors in rat brain. Likewise, Rebola et al [20] found a long-term decrease in the number of adenosine A 1 receptors in rat brain after induction of convulsions coupled with increased density of adenosine A 2A receptors.…”

Section: Discussionmentioning

confidence: 99%

E. coli lipopolysaccharide attenuates adenosine A1 receptor-mediated increase in plasma exudation from the hamster cheek pouch

Gao

Rubinstein

2010

Inflamm. Res.

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Objective and design To determine whether exposure to E. coli lipopolysaccharide (LPS) modulates adenosine A1 receptor-induced increase in plasma exudation from the intact hamster cheek pouch microcirculation. Methods and results Using intravital microscopy, we found that suffusion of R(−)-N6-(2-phenylisopropyl)-adenosine (R(−)-PIA) (1.0 and 10.0 nM), a selective adenosine A1 receptor agonist, onto the intact cheek pouch elicited significant, concentration-dependent leaky site formation and increase in clearance of fluorescein thioisocyanate-dextran (mol mass, 70 kDa) from post-capillary venules (p < 0.05). These responses were significantly attenuated by pre-treatment of hamsters with LPS (p < 0.05). By contrast, LPS had no significant effects on CGS-21680-, a selective adenosine A2A receptor agonist, bradykinin- and substance P-induced increases in plasma exudation from the cheek pouch. Conclusion These data indicate that LPS attenuates adenosine A1 receptor-induced increase in plasma exudation in vivo in a specific fashion. We suggest that this phenomenon represents an endogenous anti-inflammatory cue to avoid excessive inflammation during Gram-negative bacterial infections.

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Section: Discussionmentioning

confidence: 99%

E. coli lipopolysaccharide attenuates adenosine A1 receptor-mediated increase in plasma exudation from the hamster cheek pouch

Gao

Rubinstein

2010

Inflamm. Res.

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“…Insults of short‐duration up‐regulate A 1 R, whereas a more prolonged insult will trigger a down‐regulation of A 1 R. Whether such up‐ and down‐regulation processes depend only on the rapid A 1 R trafficking or also on a control of A 1 R expression (Ruiz et al . , ; Wetherington and Lambert ; Coelho et al . ; Hettinger et al .,, ; Roman et al .…”

Section: Role Of A1r In Neuroprotection: Prophylaxis and Preconditionmentioning

confidence: 99%

“…A last perplexing aspect was the realization that timing was critical to define when A 1 R activation affords neuroprotection: in fact, A 1 R activation attenuates brain damage when administered shortly before or simultaneously with the noxious stimuli, but A 1 R tend to lose their neuroprotective effectiveness when administered after the noxious stimuli (Sweeney 1997;von Lubitz 1999von Lubitz , 2001de Mendonc ßa et al 2000). This loss of efficiency seems to result from a desensitization of A 1 R after noxious stimuli: in fact, different noxious stimuli trigger a marked increase of extracellular adenosine levels in the brain parenchyma (Phillis et al 1991;During and Spencer 1992;Berman et al 2000;Frenguelli et al 2003Frenguelli et al , 2007Pearson et al 2006; reviewed in Dale and Frenguelli 2009;Latini and Pedata 2001) and A 1 R undergo desensitization after prolonged exposure to their agonists (Hettinger et al, 1996(Hettinger et al, , 1998Nie et al 1997;Ruiz et al 1996Ruiz et al , 2005Wetherington and Lambert 2002;Coelho et al 2006;Roman et al 2008;Jajoo et al 2010;Baines et al 2011). Such A 1 R desensitization is also likely responsible for the inversion of the therapeutic effect upon prolonged exposure to A 1 R agonists, which cause a paradoxical aggravation of brain damage (Von Lubitz et al 1994a,b;Jacobson et al 1996).…”

Section: Time-dependent Effects Of a 1 R On Neurodegenerationmentioning

confidence: 99%

“…In fact, it seems that the density and functional efficiency of A 1 R can be rapidly and bidirectionally controlled. Insults of short-duration up-regulate A 1 R, whereas a more prolonged insult will trigger a downregulation of A 1 R. Whether such up-and down-regulation processes depend only on the rapid A 1 R trafficking or also on a control of A 1 R expression (Ruiz et al 1996(Ruiz et al , 2005Wetherington and Lambert 2002;Coelho et al 2006;Hettinger et al, 1996Hettinger et al, , 1998Roman et al 2008;Jajoo et al 2010;Baines et al 2011) remains to be clarified. However, the potential of bolstering A 1 R activation as a therapeutic strategy should imply a greater interest in understanding the mechanisms controlling A 1 R trafficking and A 1 R expression, both of which are poorly understood.…”

Section: Open Questions On the Dual Effect Of A 1 R On Neurodegenerationmentioning

confidence: 99%

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How does adenosine control neuronal dysfunction and neurodegeneration?

Cunha

2016

Journal of Neurochemistry

368

385

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The adenosine modulation system mostly operates through inhibitory A 1 (A 1 R) and facilitatory A 2A receptors (A 2A R) in the brain. The activity-dependent release of adenosine acts as a brake of excitatory transmission through A 1 R, which are enriched in glutamatergic terminals. Adenosine sharpens salience of information encoding in neuronal circuits: highfrequency stimulation triggers ATP release in the 'activated' synapse, which is locally converted by ecto-nucleotidases into adenosine to selectively activate A 2A R; A 2A R switch off A 1 R and CB1 receptors, bolster glutamate release and NMDA receptors to assist increasing synaptic plasticity in the 'activated' synapse; the parallel engagement of the astrocytic syncytium releases adenosine further inhibiting neighboring synapses, thus sharpening the encoded plastic change. Brain insults trigger a large outflow of adenosine and ATP, as a danger signal. A 1 R are a hurdle for damage initiation, but they desensitize upon prolonged activation. However, if the insult is near-threshold and/or of short-duration, A 1 R trigger preconditioning, which may limit the spread of damage. Brain insults also up-regulate A 2A R, probably to bolster adaptive changes, but this heightens brain damage since A 2A R blockade affords neuroprotection in models of epilepsy, depression, Alzheimer's, or Parkinson's disease. This initially involves a control of synaptotoxicity by neuronal A 2A R, whereas astrocytic and microglia A 2A R might control the spread of damage. The A 2A R signaling mechanisms are largely unknown since A 2A R are pleiotropic, coupling to different G proteins and non-canonical pathways to control the viability of glutamatergic synapses, neuroinflammation, mitochondria function, and cytoskeleton dynamics. Thus, simultaneously bolstering A 1 R preconditioning and preventing excessive A 2A R function might afford maximal neuroprotection. Keywords: A 1 receptor, A 2A receptor, astrocyte, microglia, synaptic plasticity, synaptotoxicity. This article is part of a mini review series: "Synaptic Function and Dysfunction in Brain Diseases". Relevance of modulation systems to tune information flow in brain circuitsThe goal of understanding the flow of information in neuronal circuits has traditionally been centered in studying the key processes sustaining synaptic transmission and plasticity -i.e. the role of glutamate and glutamate receptors, as well as to a lesser extent the role of GABA and its receptors. If one considers an analogy to the experience of watching TV, this corresponds to studying how the ON/OFF button impacts all Received April 4, 2016; revised manuscript received May 23, 2016; accepted June 23, 2016. Address correspondence and reprint requests to R. A. Cunha, Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal. E-mail: cunharod@gmail.com Abbreviations used: A 1 R, adenosine A 1 receptor; A 2A R, adenosine A 2A receptor; ADHD, attention deficit and hyperactivity disorder; BDNF, brain-derived neurotrophi...

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“…Adenylyl cyclase activity was determined in plasma membranes as previously described (34,35) with minor modifications. Plasma membranes were first incubated with adenosine deaminase (ADA, 5 U/mg protein) at 37-C for 30 minutes to remove endogenous adenosine.…”

Section: Determination Of Adenylyl Cyclase Activitymentioning

confidence: 99%

Adenosine A1 Receptor Protein Levels and Activity Is Increased in the Cerebral Cortex in Creutzfeldt-Jakob Disease and in Bovine Spongiform Encephalopathy-Infected Bovine-PrP Mice

Rodríguez

Martı́n

Albasanz³

et al. 2006

Journal of Neuropathology and Experimental Neurology

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Prion diseases are characterized by neuronal loss, astrocytic gliosis, spongiform change, and abnormal protease-resistant prion protein (PrP res ) deposition. Creutzfeldt-Jakob disease (CJD) is the most prevalent human prion disease, whereas scrapie and bovine spongiform encephalopathy (BSE) are the most common animal prion diseases. Several candidates have been proposed as mediators of degeneration in prion diseases, one of them glutamate. Recent studies have shown reduced metabotropic glutamate receptor/ phospholipase C signaling in the cerebral cortex in CJD, suggesting that this important neuromodulator and neuroprotector pathway is attenuated in CJD. Adenosine is involved in the regulation of different metabolic processes under physiological and pathologic conditions. Adenosine function is mediated by adenosine receptors, which are categorized into 4 types: A 1 , A 2A , A 2B , and A 3 . A 1 Rs are G-protein-coupled receptors that induce the inhibition of adenylyl cyclase activity. The most dramatic inhibitory actions of adenosine receptors are on the glutamatergic system. For these reasons, we examined the levels of A 1 Rs in the frontal cortex of 12 patients with CJD and 6 age-matched controls and in BSE-infected bovine-PrP transgenic mice (BoPrP-Tg110 mice) at different postincubation times to address modifications in A 1 Rs with disease progression. A significant increase in the protein levels of A 1 Rs was found in the cerebral cortex in CJD and in the murine BSE model at advanced stages of the disease and coincidental with the appearance of PrP res expression. In addition, the activity of A 1 Rs was analyzed by in vitro assays with isolated membranes of the frontal cortex in CJD. Increased activity of the receptor, as revealed by the decreased forskolin-stimulated cAMP production in response to the A 1 R agonists cyclohexyl adenosine and cyclopentyl adenosine, was observed in CJD cases when compared with controls. Finally, mRNA A 1 R levels were similar in CJD and control cases, thus suggesting abnormal A 1 R turnover or dysregulation of raft-associated signaling pathways in CJD. These results show, for the first time, sensitization of A 1 Rs in prion diseases.

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Different modulation of inhibitory and stimulatory pathways mediated by adenosine after chronic in vivo agonist exposure

Cited by 10 publications

References 41 publications

E. coli lipopolysaccharide attenuates adenosine A1 receptor-mediated increase in plasma exudation from the hamster cheek pouch

E. coli lipopolysaccharide attenuates adenosine A1 receptor-mediated increase in plasma exudation from the hamster cheek pouch

How does adenosine control neuronal dysfunction and neurodegeneration?

Adenosine A1 Receptor Protein Levels and Activity Is Increased in the Cerebral Cortex in Creutzfeldt-Jakob Disease and in Bovine Spongiform Encephalopathy-Infected Bovine-PrP Mice

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