Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • 2024-04
  • 2024-05
  • 2024-06
  • 2024-07
  • Another interesting interaction concerns NMDA preconditionin

    2024-06-14

    Another interesting interaction concerns NMDA preconditioning to protect against glutamate neurotoxicity. It has been shown that an A1R antagonist prevented neuroprotection evoked by NMDA preconditioning against glutamate-induced cellular damage in cerebellar granule cells. In this study, the functionality of A1Rs was not affected by NMDA preconditioning, but this treatment promoted A2AR desensitization in concert with A1R activation [7]. These results are in line with other studies indicating that adenosine down regulates excitatory and inhibitory synaptic transmission in several akt inhibitor areas through activation of A1Rs and A2AR [21,58]. Furthermore, activation of A1Rs mediates reversal of long-term potentiation (LTP) produced by brief application of NMDA in hippocampal CA1 neurons [41]. Finally, it has recently been demonstrated that A2ARs receptors localized in striatal glutamatergic terminals play a very important role in control of striatal glutamate release [12,13]. These receptors form heteromers with A1Rs, and the A1R–A2AR heteromer constitutes a “concentration-dependent switch” that regulates glutamate release depending on the extracellular concentration of adenosine. Thus, low concentrations of adenosine inhibit glutamate release by stimulating the A1Rs, while higher concentrations induce glutamate release by also stimulating A2AR, which shuts down A1R signaling by means of an antagonistic intramembrane receptor interaction [25]. However, the A2ARs-dependent modulation of glutamate release seems to be under an inhibitory control by co-localized D2Rs. Taken together, there are several ways in which adenosine may interact synergistic with glutamatergic neurotransmission. Adenosine can affect glutamatergic transmission via A1Rs or A2ARs. NMDA receptors and A1Rs to down regulate glutamate release presynaptically in pyramidal cells of the cingulate cortex [9], neurons of the hippocampus [74], and striatal neurons [75]. Another putative mechanism is the elevation of the threshold to open NMDA receptor-operated channels by antagonizing membrane depolarization [85].
    Fast synaptic inhibition in the brain and spinal cord is largely mediated by GABAA receptors that are also targeted by drugs such as benzodiazepines, barbiturates, neurosteroids and some anesthetics. The modulation of their function will have important consequences for neuronal excitation [43]. One accepted mean of modifying the efficacy is a functional interaction with adenosine. Cristovao-Ferreira et al. [14] showed that GABA uptake by astrocytes is under modulation by extracellular adenosine. They found that A1R–A2AR heteromers in astrocytes regulating GABA transport in an opposite way, with A1R mediating inhibition of GABA transport and A2AR mediating facilitation of GABA transport. This A1R–A2AR functional unit may, therefore, operate as a dual amplifier to control ambient GABA levels at synapses. In addition, adenosine may have an effect on either GABA release in interneurons and/or on GABAA receptors in projection neurons. The site of action may be studied electrophysiologically by inducing fast inhibitory postsynaptic potentials or application of GABA directly onto the cell. Adenosine and selective A1R agonists reduced the amplitude of the inhibitory postsynaptic potentials in lateral amygdala slice preparations. The effect was blocked by an A1R antagonist, indicating an interaction of A1Rs with GABA receptors. Additionally, adenosine did not block currents evoked by local application of GABA [38]. Thus, the modulatory effect of adenosine on the GABAergic neurotransmission appears to take place directly by inhibiting GABA release from nerve terminals [38,77]. The assumption that the activation of A1Rs can modulate inhibitory postsynaptic responses agrees with findings in several brain areas, such as the thalamus [80], suprachiasmatic and arcuate nucleus [60], and substantia nigra pars compacta [77]. There is some evidence that activation of A1Rs is also involved in GABAA receptor down-regulation, implying a facilitation of the neurotransmission. The GABA-induced neurotransmission was significantly reduced be adenosine via activation of A1Rs [47]. The mode of this interaction seems due to a regulation of the GABAA chloride channel [5].