Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/4845
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dc.contributor.authorAmbrósio, António F.-
dc.contributor.authorSilva, Ana P.-
dc.contributor.authorMalva, João O.-
dc.contributor.authorSoares-da-Silva, Patrício-
dc.contributor.authorCarvalho, Arsélio P.-
dc.contributor.authorCarvalho, Caetana M.-
dc.date.accessioned2008-09-01T14:15:27Z-
dc.date.available2008-09-01T14:15:27Z-
dc.date.issued1999en_US
dc.identifier.citationNeuropharmacology. 38:9 (1999) 1349-1359en_US
dc.identifier.urihttps://hdl.handle.net/10316/4845-
dc.description.abstractIn order to better understand the mechanism(s) of action of carbamazepine (CBZ), we studied its effects on the increase in [Ca2+]i and [Na+]i stimulated by glutamate ionotropic receptor agonists, in cultured rat hippocampal neurons, as followed by indo-1 or SBFI fluorescence, respectively. CBZ inhibited the increase in [Ca2+]i stimulated either by glutamate, kainate, [alpha]-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA), or N-methyl--aspartate (NMDA), in a concentration-dependent manner. In order to discriminate the effects of CBZ on the activation of glutamate receptors from possible effects on Ca2+ channels, we determined the inhibitory effects of Ca2+ channel blockers on [Ca2+]i changes in the absence or in the presence of CBZ. The presence of 1 [mu]M nitrendipine, 0.5 [mu]M [omega]-conotoxin GVIA ([omega]-CgTx GVIA), or of both blockers, inhibited the kainate-stimulated increase in [Ca2+]i by 51.6, 32.9 or 68.7%, respectively. In the presence of both 100 [mu]M CBZ and nitrendipine, the inhibition was similar (54.1%) to that obtained with nitrendipine alone, but in the presence of both CBZ and [omega]-CgTx GVIA, the inhibition was greater (54%) than that caused by [omega]-CgTx GVIA alone. However, CBZ did not inhibit the increase in [Na+]i stimulated by the glutamate receptor agonists, but inhibited the increase in [Na+]i due to veratridine. Tetrodotoxin, or MK-801, did not inhibit the influx of Na+ stimulated by kainate, indicating that Na+ influx occurs mainly through the glutamate ionotropic non-NMDA receptors. Moreover, LY 303070, a specific AMPA receptor antagonist, inhibited the [Na+]i response to kainate or AMPA by about 70 or 80%, respectively, suggesting that AMPA receptors are mainly involved. Taken together, the results suggest that CBZ inhibits L-type Ca2+ channels and Na+ channels, but does not inhibit activation of glutamate ionotropic receptors.en_US
dc.description.urihttp://www.sciencedirect.com/science/article/B6T0C-3X1W5Y4-D/1/65c32835840a01052a606b944eb4cabden_US
dc.format.mimetypeaplication/PDFen
dc.language.isoengeng
dc.rightsopenAccesseng
dc.subjectCarbamazepineen_US
dc.subjectGlutamate ionotropic receptorsen_US
dc.subjectKainateen_US
dc.subjectVoltage-sensitive Ca2+ channelsen_US
dc.subjectVoltage-sensitive Na+ channelsen_US
dc.subject[Ca2+]ien_US
dc.titleCarbamazepine inhibits L-type Ca2+ channels in cultured rat hippocampal neurons stimulated with glutamate receptor agonistsen_US
dc.typearticleen_US
dc.identifier.doi10.1016/S0028-3908(99)00058-1-
item.fulltextCom Texto completo-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextopen-
item.languageiso639-1en-
item.openairetypearticle-
item.cerifentitytypePublications-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.orcid0000-0002-0477-1641-
crisitem.author.orcid0000-0002-5438-4447-
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
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