The hallucinogen 2,5-dimethoxy-4-iodoamphetamine hydrochloride activates neurotrophin receptors in a neuronal cell line and promotes neurites extension.
J Neural Transm (Vienna)
; 124(6): 749-759, 2017 06.
Article
em En
| MEDLINE
| ID: mdl-28315978
ABSTRACT
Decreased neurotrophic factors expression and neurotrophin receptors signalling have repeatedly been reported in association with stress, depression, and neurodegenerative disorders. We have previously identified the hallucinogen 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) as protective against trophic deprivation-induced cytotoxicity in human neuroblastoma SK-N-SH cells and established the dependence of this effect on the 5-HT2A receptor, tyrosine kinases activity, and the extracellular signal-regulated kinase pathway. In the current study, we investigated the effect of DOI on tropomyosin-related kinase receptor A (TrkA) phosphorylation. Treatment with DOI increased TrkA tyrosine phosphorylation in SK-N-SH cells, determined by immunoprecipitation with TrkA antibody and immunoblotting with anti-phosphotyrosine- and TrkA-antibodies. Analysis of DOI's effect on individual TrkA residues in SK-N-SH cells showed that it increases TrkA Tyr490 phosphorylation (177 ± 23% after 5 µM DOI for 30 min compared to vehicle). Furthermore, DOI treatment increased the percentage of SK-N-SH cells extending neurites in a TrkA-dependent manner (17.2 ± 2.2% after 5 µM DOI treatment for 6 days compared to 5.6 ± 1.7% after vehicle). In a different cell model-lymphoblastoid cell lines-DOI treatment increased tropomyosin-related kinase receptor B (TrkB) phosphorylation, determined by immunoprecipitation with TrkB antibody and immunoblotting with anti-phosphotyrosine antibody and total Trk antibody. Our results identify the Trk receptors as a downstream target of the hallucinogen DOI. In light of the known involvement of Trk receptors in mental diseases, their participation in DOI-mediated effects warrants further investigation.
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Base de dados:
MEDLINE
Assunto principal:
Neuritos
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Receptor trkA
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Receptor trkB
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Crescimento Neuronal
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Alucinógenos
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Anfetaminas
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article