Adenosine by activating A1 receptors prevents GABAA-mediated actions during hypoxia in the rat hippocampus

Lucchi, R.; Latini, Serena; Mendonça, Alexandre de; Sebastião, Ana M.; Ribeiro, Joaquim A.

doi:10.1016/0006-8993(96)00748-2

Cited by 28 publications

(24 citation statements)

References 18 publications

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“…IL-6, neuronal adenosine A 1 receptor and brain function K Biber et al experiment, we induced a longer hypoxic period (4 min), sufficient to cause a mild depression of synaptic transmission even in control conditions (33.3%) and the response to hypoxia was still more pronounced (67.5%) in a slice taken from the same hippocampus previously exposed to IL-6 (10 U/ml) for 6 h. Since prolonged hypoxic periods cause an inhibition of synaptic transmission that results from both adenosine A 1 receptor-dependent and -independent mechanisms (Lucchi et al, 1996), we further investigated if the later were also influenced by IL-6. As shown in Figure 3c Influence of IL-6 on Adenosine A 1 Receptor Actions Upon Excitoxicity IL-6 increases the function and neuroprotective properties of postsynaptic adenosine A 1 receptors against glutamateinduced neurotoxicity.…”

Section: Resultsmentioning

confidence: 91%

Interleukin-6 Upregulates Neuronal Adenosine A1 Receptors: Implications for Neuromodulation and Neuroprotection

Biber

Pinto-Duarte

Wittendorp

et al. 2007

Neuropsychopharmacol

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The immunological response in the brain is crucial to overcome neuropathological events. Some inflammatory mediators, such as the immunoregulatory cytokine interleukin-6 (IL-6) affect neuromodulation and may also play protective roles against various noxious conditions. However, the fundamental mechanisms underlying the long-term effects of IL-6 in the brain remain unclear. We now report that IL-6 increases the expression and function of the neuronal adenosine A 1 receptor, with relevant consequences to synaptic transmission and neuroprotection. IL-6-induced amplification of A 1 receptor function enhances the responses to readily released adenosine during hypoxia, enables neuronal rescue from glutamate-induced death, and protects animals from chemically induced convulsing seizures. Taken together, these results suggest that IL-6 minimizes the consequences of excitotoxic episodes on brain function through the enhancement of endogenous adenosinergic signaling.

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Section: Resultsmentioning

confidence: 91%

Interleukin-6 Upregulates Neuronal Adenosine A1 Receptors: Implications for Neuromodulation and Neuroprotection

Biber

Pinto-Duarte

Wittendorp

et al. 2007

Neuropsychopharmacol

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“…This contrasts with the presynaptic inhibitory role of A 1 receptor activation in hypoxia (Lucchi et al, 1996) or hypoglycemia conditions (Fowler, 1993b) in different models, and with the known deleterious role of acutely applied adenosine A 1 receptor antagonists in ischemic injury models (for a review, see Rudolphi et al, 1992). Previous studies in retinal preparations have demonstrated that adenosine can tonically activate inhibitory A 1 receptors (Larsen and Osborne, 1996) and that activation of A 1 receptors inhibits NMDA currents (Costenla et al, 1999), a central event in ischemic neuronal damage in the retina (Yoon and Marmor, 1989).…”

Section: Discussionmentioning

confidence: 77%

“…It remains to be explored if the role of the GABAergic system in the control of excitatory amino acid release may burst upon blockade of the adenosine system, as has been shown to occur in the modulation of hypoxia-induced depression of synaptic transmission in hippocampal slices (Lucchi et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Adenosine A2AReceptors Regulate the Extracellular Accumulation of Excitatory Amino Acids upon Metabolic Dysfunction in Chick Cultured Retinal Cells

Rego

Agostinho

Melo

et al. 2000

Experimental Eye Research

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The role of endogenous extracellular adenosine as a tonic modulator of the extracellular accumulation of excitatory amino acids (glutamate and aspartate) caused by metabolic inhibition was investigated in cultured retinal cells. The selective adenosine A2A receptor antagonist, 4-[2-[7-amino-2-(2-furyl)(1,2,4)-triazin-5-ylamino]-ethyl]ph enol (ZM241385) (50 nM), increased the release of glutamate (three- to four-fold) and of aspartate (nearly two-fold) upon iodoacetic acid-induced glycolysis inhibition, in the presence or in the absence of Ca2+. Blockade of tonic activation of A2A receptors by ZM241385 also increased (nearly two-fold) the ischemia-induced release of glutamate and aspartate. Furthermore, another selective A2A receptor antagonist, 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5- c] pyrimidine (SCH58261), also increased the release of aspartate and glutamate by about two-fold in cells submitted to glycolysis inhibition. In contrast, the selective adenosine A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (100 nM), did not significantly modify the extracellular accumulation of either glutamate or aspartate caused by inducers of chemical ischemia or glycolytic inhibitors. Inhibition of glycolysis also increased (about three-fold) the extracellular accumulation of GABA, which was virtually unchanged by ZM241385. Furthermore, the GABAA receptor antagonist, bicuculline (10 microM), only increased (nearly two-fold) the iodoacetic acid-induced Ca(2+)-dependent release of glutamate, whereas the GABAB receptor antagonist, 3-aminopropyl(diethoxymethyl) phosphinic acid, CGP35348 (100 microM), was devoid of effects on the extracellular accumulation of glutamate and aspartate. These results show that endogenous extracellular adenosine, which rises under conditions of inhibited glycolysis, tonically inhibits the extracellular accumulation of excitatory amino acid through the activation of A2A, but not A1, adenosine receptors, and this effect is independent of GABAA and GABAB functions in the cultured retinal cells.

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“…After application of hypoxia for 15 min, a complete depression of synaptic transmission occurs without any modification in the presence of the GABA A antagonist picrotoxin. However, if we apply the same hypoxic conditions in the presence of the A 1 antagonist DPCPX, the depression in synaptic transmission is greatly attenuated and this was further attenuated if we applied the same procedure in the presence of picrotoxin, suggesting that GABA A receptors participate in the process of hypoxiainduced synaptic inhibition when the adenosine A 1 receptors are blocked [Lucchi et al, 1996].…”

Section: A 1 With Gaba a Receptorsmentioning

confidence: 99%

Adenosine receptor interactions in the hippocampus

Ribeiro¹,

Cunha‐Reis²,

Lopes³

et al. 2001

Drug Development Research

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Adenosine receptors are involved in interactions with receptors for other neurotransmitters and/or neuromodulators. This opens novel possibilities for the action of this nucleoside. Either through direct receptor-receptor modulation or beyond the receptor level (PKA, PKC, or calcium channels), it appears that to protect the cells from insult adenosine moves around to use as many several receptor systems as possible, namely, receptors for neuropeptides (CGRP and VIP), ionotropic (NMDA) and metabotropic (mGlur I and III) glutamate receptors, GABA, and nicotinic autofacilitatory, muscarinic, and dopamine receptors. With these, adenosine might synchronize or desynchronize synaptic transmission in order to finetune the nervous system. Drug Dev. Res. 52:337-345, 2001.

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Adenosine by activating A1 receptors prevents GABAA-mediated actions during hypoxia in the rat hippocampus

Cited by 28 publications

References 18 publications

Interleukin-6 Upregulates Neuronal Adenosine A1 Receptors: Implications for Neuromodulation and Neuroprotection

Interleukin-6 Upregulates Neuronal Adenosine A1 Receptors: Implications for Neuromodulation and Neuroprotection

Adenosine A2AReceptors Regulate the Extracellular Accumulation of Excitatory Amino Acids upon Metabolic Dysfunction in Chick Cultured Retinal Cells

Adenosine receptor interactions in the hippocampus

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