Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/27660
DC Field | Value | Language |
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dc.contributor.author | Ferreira, S. G. | - |
dc.contributor.author | Gonçalves, F. Q. | - |
dc.contributor.author | Marques, J. M. | - |
dc.contributor.author | Tomé, Â. R. | - |
dc.contributor.author | Rodrigues, R. J. | - |
dc.contributor.author | Nunes-Correia, I. | - |
dc.contributor.author | Ledent, C. | - |
dc.contributor.author | Harkany, T. | - |
dc.contributor.author | Venance, L. | - |
dc.contributor.author | Cunha, R. A. | - |
dc.contributor.author | Köfalvi, A. | - |
dc.date.accessioned | 2014-11-17T15:30:57Z | - |
dc.date.available | 2015-11-18T03:00:06Z | - |
dc.date.issued | 2014 | - |
dc.identifier.citation | FERREIRA, S. G. [et. al] - Presynaptic A2A adenosine receptors dampen CB1 cannabinoid receptor-mediated inhibition of corticostriatal glutamatergic transmission. "British Journal of Pharmacology". ISSN 1476-5381. (2014) | por |
dc.identifier.issn | 1476-5381 | - |
dc.identifier.uri | https://hdl.handle.net/10316/27660 | - |
dc.description.abstract | Background and Purpose Both CB1 cannabinoid and A2A adenosine receptors (CB1Rs and A2ARs) control synaptic transmission at corticostriatal synapses, with great therapeutic importance for neurological and psychiatric disorders. A post-synaptic CB1R-A2AR interaction has already been unraveled, but the presynaptic A2AR-mediated control of presynaptic neuromodulation by CB1Rs remains to be defined. Since the corticostriatal terminals provide the major input of the basal ganglia, understanding the interactive nature of converging neuromodulation on them will provide us with novel powerful tools to understand the physiology of corticostriatal synaptic transmission and interpret changes associated with pathological conditions. Experimental Approach Here we employ selective presynaptic tools to study the putative presynaptic interaction between the two neuromodulator systems. Pharmacological manipulation of CB1R and A2AR was carried out in isolated nerve terminals used for flow synaptometry, immunoprecipitation, radioligand binding, ATP and glutamate release measurement, as well as in whole-cell patch-clamp recordings in horizontal corticostriatal slices. Results Flow synaptometry showed that A2AR are extensively co-localized with CB1R-immunopositive corticostriatal terminals, and A2AR co-immunoprecipitated CB1R in these purified terminals. A2AR activation decreased CB1R radioligand binding and decreased the CB1R-mediated inhibition of high-K+-evoked glutamate release in corticostriatal terminals. Accordingly, A2AR activation prevented CB1R-mediated paired-pulse facilitation and attenuated the CB1R-mediated inhibition of synaptic transmission in glutamatergic synapses of corticostriatal slices. Conclusions and Implications These results show that presynaptic A2AR dampens CB1R-mediated inhibition of corticostriatal terminals. This constitutes a thus far unrecognized mechanism to shut-down the potent CB1R-mediated presynaptic inhibition, enabling a frequency-dependent enhancement of synaptic efficacy at corticostriatal synapses. | por |
dc.language.iso | eng | por |
dc.publisher | John Wiley & Sons, Inc. | por |
dc.rights | embargoedAccess | por |
dc.title | Presynaptic A2A adenosine receptors dampen CB1 cannabinoid receptor-mediated inhibition of corticostriatal glutamatergic transmission | por |
dc.type | article | por |
degois.publication.title | British Journal of Pharmacology | por |
dc.relation.publisherversion | http://onlinelibrary.wiley.com/doi/10.1111/bph.12970/abstract | por |
dc.peerreviewed | Yes | por |
dc.identifier.doi | 10.1111/bph.12970 | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.openairetype | article | - |
item.cerifentitytype | Publications | - |
item.grantfulltext | open | - |
item.fulltext | Com Texto completo | - |
item.languageiso639-1 | en | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0001-8671-989X | - |
crisitem.author.orcid | 0000-0003-2550-6422 | - |
Appears in Collections: | FMUC Medicina - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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File | Description | Size | Format | |
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Presynaptic.pdf | 1.18 MB | Adobe PDF | View/Open |
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