ArticleCNS neuroscience & therapeutics2016
Protein Kinases Alter the Allosteric Modulation of the Serotonin Transporter In Vivo and In Vitro.
Article in CNS neuroscience & therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed, 5 citations in OpenAlex.
- Is It Time to Use Modeling of Cellular Transporter Homeostasis to Inform Drug-Drug Interaction Studies: Theoretical Considerations.The AAPS journal · 2021Article
- Outside the brain: an inside view on transgenic animal and stem cell-based models to examine neuronal serotonin-dependent regulation of HPA axis-controlled events during development and adult stages.Stem cell investigation · 2016Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimStudies using S- and R-enantiomers of the SSRI citalopram have shown that R-citalopram exerts an antagonistic effect on the efficacy of the antidepressant S-citalopram (escitalopram) through an interaction at an allosteric modulator site on the serotonin transporter (SERT). Here, we show that protein kinase signaling systems are involved in the allosteric modulation of the SERT in vivo and in vitro.
methodsWe assessed the effects of nonspecific protein kinase inhibitor staurosporine in the action of escitalopram and/or R-citalopram using electrophysiological and behavioral assays in rats and cell surface SERT expression measures in serotoninergic cells.
resultsAcute administration of R-citalopram counteracted the escitalopram-induced suppression of the serotonin (5-HT) neuronal firing activity and increase of the head twitches number following L-5-hydroxytryptophan injection. Importantly, these counteracting effects of R-citalopram were abolished by prior systemic administration of staurosporine. Interestingly, the preventing effect of staurosporine on 5-HT neuronal firing activity was abolished by direct activation of protein kinase C with phorbol 12-myristate 13-acetate. Finally, in vitro, quantification of the amount of cell surface-expressed SERT molecules revealed that R-citalopram prevented escitalopram-induced SERT internalization that was completely altered by staurosporine.
conclusionTaken together, these results highlight for the first time an involvement of protein kinases in the allosteric modulation of SERT function.
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