β-Phenylethylamine requires the dopamine transporter to increase extracellular dopamine in Caenorhabditis elegans dopaminergic neurons.

Autor: Hossain M; Department of Basic Science, University of North Dakota, School of Medicine and Health Sciences, Grand Forks, ND 58202-9037, United States., Wickramasekara RN; Department of Basic Science, University of North Dakota, School of Medicine and Health Sciences, Grand Forks, ND 58202-9037, United States., Carvelli L; Department of Basic Science, University of North Dakota, School of Medicine and Health Sciences, Grand Forks, ND 58202-9037, United States. Electronic address: lucia.carvelli@med.und.edu.
Jazyk: angličtina
Zdroj: Neurochemistry international [Neurochem Int] 2014 Jul; Vol. 73, pp. 27-31. Date of Electronic Publication: 2013 Oct 23.
DOI: 10.1016/j.neuint.2013.10.010
Abstrakt: β-Phenylethylamine (βPEA) is an endogenous amine that has been shown to increase the synaptic levels of dopamine (DA). A number of in vitro and behavioral studies suggest the dopamine transporter (DAT) plays a role in the effects generated by βPEA, however the mechanism through which βPEA affects DAT has not yet been elucidated. Here, we used Caenorhabditis (C.) elegans DAT (DAT-1) expressing LLC-pk1 cells and neuronal cultures to investigate whether the βPEA-induced increase of extracellular DA required DAT-1. Our data show that βPEA increases extracellular dopamine both in DAT-1 transfected cells and cultures of differentiated neurons. RTI-55, a cocaine homologue and DAT inhibitor, completely blocked the βPEA-induced effect in transfected cells. However in neuronal cultures, RTI-55 only partly inhibited the increase of extracellular DA generated by βPEA. These results suggest that βPEA requires DAT-1 and other, not yet identified proteins, to increase extracellular DA when tested in a native system. Furthermore, our results suggest that βPEA-induced increase of extracellular DA does not require functional monoamine vesicles as genetic ablation of the C. elegans homologue vesicular monoamine transporter, cat-1, did not compromise the ability of βPEA to increase extracellular DA. Finally, our electrophysiology data show that βPEA caused fast-rising and self-inactivating amperometric currents in a subset of wild-type DA neurons but not in neurons isolated from dat-1 knockout animals. Taken together, these data demonstrate that in both DA neurons and heterogeneous cultures of differentiated C. elegans neurons, βPEA releases cytoplasmic DA through DAT-1 to ultimately increase the extracellular concentration of DA.
(Copyright © 2013 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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