Functional interaction between pre‐synaptic <scp>α6β2</scp>‐containing nicotinic and adenosine <scp>A<sub>2A</sub></scp> receptors in the control of dopamine release in the rat striatum

Garção, Pedro; Szabó, Eszter; Wopereis, Sandro; Castro, Adalberto A.; Tomé, Ângelo R.; Prediger, Rui Daniel; Cunha, Rodrigo A.; Agostinho, Paula; Köfalvi, Attila

doi:10.1111/bph.12234

Cited by 31 publications

(22 citation statements)

References 79 publications

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“…One possibility would be a direct heteromerisation between A 2B R and A 1 R, given that A 2B R can heteromerise with different membrane proteins such as receptors (Corset et al ., ; Moriyama & Sitkovsky, ) and enzymes (Antonioli et al ., ) and A 1 R can also form dimers with different G‐protein‐coupled receptors (Gines et al ., ; Ciruela et al ., ; Kamikubo et al ., ). An alternative would be an ability of A 2B R to trigger an intracellular cross talk through its diverse G‐protein coupling (Ryzhov et al ., ; Cohen et al ., ; Liu et al ., ) to functionally desensitise A 1 R (Ciruela et al ., ; Nie et al ., ; Hashimi et al ., ; Lopes et al ., ), in a manner analogous to the ability of A 2B R to control ion channels (Garção et al ., ), G protein coupled receptors (Feoktistov & Biaggioni, ; Conde et al ., ) or growth factor receptors (Corset et al ., ). Further studies will be required to clarify the mechanism underlying the ability of A 2B R to functionally desensitise A 1 R in nerve terminals.…”

Section: Discussionmentioning

confidence: 99%

“…This is fuelled by the observation that A 2B R display a lower affinity for adenosine than the other adenosine receptors (Fredholm et al ., ), suggesting that A 2B R may be preferentially activated under noxious conditions associated with higher extracellular levels of adenosine (Dunwiddie & Masino, ; Popoli & Pepponi, ). However, some studies suggest that A 2B R might also control neurotransmitter release through interaction with other receptors (Moriyama & Sitkovsky, ; Garção et al ., ).…”

Section: Introductionmentioning

confidence: 97%

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Adenosine A_2b receptors control A₁ receptor‐mediated inhibition of synaptic transmission in the mouse hippocampus

Gonçalves

Pires

Pliássova

et al. 2015

Eur J of Neuroscience

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Adenosine is a neuromodulator mostly acting through A1 (inhibitory) and A2A (excitatory) receptors in the brain. A2B receptors (A(2B)R) are G(s/q)--protein-coupled receptors with low expression in the brain. As A(2B)R function is largely unknown, we have now explored their role in the mouse hippocampus. We performed electrophysiological extracellular recordings in mouse hippocampal slices, and immunological analysis of nerve terminals and glutamate release in hippocampal slices and synaptosomes. Additionally, A(2B)R-knockout (A(2B)R-KO) and C57/BL6 mice were submitted to a behavioural test battery (open field, elevated plus-maze, Y-maze). The A(2B)R agonist BAY60-6583 (300 nM) decreased the paired-pulse stimulation ratio, an effect prevented by the A(2B)R antagonist MRS 1754 (200 nM) and abrogated in A(2B)R-KO mice. Accordingly, A(2B)R immunoreactivity was present in 73 ± 5% of glutamatergic nerve terminals, i.e. those immunopositive for vesicular glutamate transporters. Furthermore, BAY 60-6583 attenuated the A(1)R control of synaptic transmission, both the A(1)R inhibition caused by 2-chloroadenosine (0.1-1 μM) and the disinhibition caused by the A(1)R antagonist DPCPX (100 nM), both effects prevented by MRS 1754 and abrogated in A(2B)R-KO mice. BAY 60-6583 decreased glutamate release in slices and also attenuated the A(1)R inhibition (CPA 100 nM). A(2B)R-KO mice displayed a modified exploratory behaviour with an increased time in the central areas of the open field, elevated plus-maze and the Y-maze and no alteration of locomotion, anxiety or working memory. We conclude that A(2B)R are present in hippocampal glutamatergic terminals where they counteract the predominant A(1)R-mediated inhibition of synaptic transmission, impacting on exploratory behaviour.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Adenosine A_2b receptors control A₁ receptor‐mediated inhibition of synaptic transmission in the mouse hippocampus

Gonçalves

Pires

Pliássova

et al. 2015

Eur J of Neuroscience

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“…A 2A R are mostly located in glutamatergic synapses, 153 although they have been shown in other synapses, such as GABAergic 146,154,155 (Fig. 4C), dopaminergic, 156,157 cholinergic, 158,159 serotoninergic, 160,161 or noradrenergic synapses. 162 Adenosine levels are tightly controlled by a complex machinery of enzymes.…”

Section: The Modulation Of Aged Synapse By Adenosine a 2a Receptorsmentioning

confidence: 93%

Novel Players in the Aging Synapse: Impact on Cognition

Temido‐Ferreira

Coelho

Pousinha

et al. 2019

Journal of Caffeine and Adenosine Research

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While neuronal loss has long been considered as the main contributor to age-related cognitive decline, these alterations are currently attributed to gradual synaptic dysfunction driven by calcium dyshomeostasis and alterations in ionotropic/metabotropic receptors. Given the key role of the hippocampus in encoding, storage, and retrieval of memory, the morpho-and electrophysiological alterations that occur in the major synapse of this network-the glutamatergic-deserve special attention. We guide you through the hippocampal anatomy, circuitry, and function in physiological context and focus on alterations in neuronal morphology, calcium dynamics, and plasticity induced by aging and Alzheimer's disease (AD). We provide state-of-the art knowledge on glutamatergic transmission and discuss implications of these novel players for intervention. A link between regular consumption of caffeine-an adenosine receptor blocker-to decreased risk of AD in humans is well established, while the mechanisms responsible have only now been uncovered. We review compelling evidence from humans and animal models that implicate adenosine A 2A receptors (A 2A R) upsurge as a crucial mediator of age-related synaptic dysfunction. The relevance of this mechanism in patients was very recently demonstrated in the form of a significant association of the A 2A R-encoding gene with hippocampal volume (synaptic loss) in mild cognitive impairment and AD. Novel pathways implicate A 2A R in the control of mGluR5-dependent NMDAR activation and subsequent Ca 2+ dysfunction upon aging. The nature of this receptor makes it particularly suited for long-term therapies, as an alternative for regulating aberrant mGluR5/NMDAR signaling in aging and disease, without disrupting their crucial constitutive activity.

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“…Baseline effect of treatments was compared to the appropriate control baseline levels in the presence of DMSO vehicle at a given time point, and expressed as a % change as above. The principle of effect size calculations was reported earlier by Garção et al (2013). Normalized data were tested for normal distribution by the KolmogoroveSmirnov test.…”

Section: Data Presentationmentioning

confidence: 99%

Lack of presynaptic interaction between glucocorticoid and CB1 cannabinoid receptors in GABA- and glutamatergic terminals in the frontal cortex of laboratory rodents

Bitencourt

Alpár

Cinquina

et al. 2015

Neurochemistry International

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Corticosteroid and endocannabinoid actions converge on prefrontocortical circuits associated with neuropsychiatric illnesses. Corticosteroids can also modulate forebrain synapses by using endocannabinoid effector systems. Here, we determined whether corticosteroids can modulate transmitter release directly in the frontal cortex and, in doing so, whether they affect presynaptic CB1 cannabinoid receptor- (CB1R) mediated neuromodulation. By Western blotting of purified subcellular fractions of the rat frontal cortex, we found glucocorticoid receptors (GcRs) and CB1Rs enriched in isolated frontocortical nerve terminals (synaptosomes). CB1Rs were predominantly presynaptically located while GcRs showed preference for the post-synaptic fraction. Additional confocal microscopy analysis of cortical and hippocampal regions revealed vesicular GABA transporter-positive and vesicular glutamate transporter 1-positive nerve terminals endowed with CB1R immunoreactivity, apposing GcR-positive post-synaptic compartments. In functional transmitter release assay, corticosteroids, corticosterone (0.1-10 microM) and dexamethasone (0.1-10 microM) did not significantly affect the evoked release of [(3)H]GABA and [(14)C]glutamate in superfused synaptosomes, isolated from both rats and mice. In contrast, the synthetic cannabinoid, WIN55212-2 (1 microM) diminished the release of both [(3)H]GABA and [(14)C]glutamate, evoked with various depolarization paradigms. This effect of WIN55212-2 was abolished by the CB1R neutral antagonist, O-2050 (1 microM), and was absent in the CB1R KO mice. CB2R-selective agonists did not affect the release of either neurotransmitter. The lack of robust presynaptic neuromodulation by corticosteroids was unchanged upon either CB1R activation or genetic inactivation. Altogether, corticosteroids are unlikely to exert direct non-genomic presynaptic neuromodulation in the frontal cortex, but they may do so indirectly, via the stimulation of trans-synaptic endocannabinoid signaling.

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Functional interaction between pre‐synaptic α6β2‐containing nicotinic and adenosine A_2A receptors in the control of dopamine release in the rat striatum

Abstract: These results provide the first evidence for a functional interaction between nicotinic and adenosine A2A R in striatal dopaminergic terminals, with likely therapeutic consequences for smoking, Parkinson's disease and other dopaminergic disorders.

Cited by 31 publications

References 79 publications

Adenosine A_2b receptors control A₁ receptor‐mediated inhibition of synaptic transmission in the mouse hippocampus

Adenosine A_2b receptors control A₁ receptor‐mediated inhibition of synaptic transmission in the mouse hippocampus

Novel Players in the Aging Synapse: Impact on Cognition

Lack of presynaptic interaction between glucocorticoid and CB1 cannabinoid receptors in GABA- and glutamatergic terminals in the frontal cortex of laboratory rodents

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Functional interaction between pre‐synaptic α6β2‐containing nicotinic and adenosine A2A receptors in the control of dopamine release in the rat striatum

Abstract: These results provide the first evidence for a functional interaction between nicotinic and adenosine A2A R in striatal dopaminergic terminals, with likely therapeutic consequences for smoking, Parkinson's disease and other dopaminergic disorders.

Cited by 31 publications

References 79 publications

Adenosine A2b receptors control A1 receptor‐mediated inhibition of synaptic transmission in the mouse hippocampus

Adenosine A2b receptors control A1 receptor‐mediated inhibition of synaptic transmission in the mouse hippocampus

Novel Players in the Aging Synapse: Impact on Cognition

Lack of presynaptic interaction between glucocorticoid and CB1 cannabinoid receptors in GABA- and glutamatergic terminals in the frontal cortex of laboratory rodents

Contact Info

Product

Resources

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Functional interaction between pre‐synaptic α6β2‐containing nicotinic and adenosine A_2A receptors in the control of dopamine release in the rat striatum

Adenosine A_2b receptors control A₁ receptor‐mediated inhibition of synaptic transmission in the mouse hippocampus

Adenosine A_2b receptors control A₁ receptor‐mediated inhibition of synaptic transmission in the mouse hippocampus