In vitro exposure to ambient fine and ultrafine particles alters dopamine uptake and release, and D2 receptor affinity and signaling

•Fine (FP) and ultrafine (UFP) particles inhibit dopamine uptake and enhance release by striatal synaptosomes.•FP and UFP increase the affinity of D2 receptors (D2Rs) for dopamine.•FP and UFP increase the potency of D2R agonists to inhibit cAMP formation.•FP and UFP particles can directly affect dop...

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Published in:Environmental toxicology and pharmacology 2020-11, Vol.80, p.103484, Article 103484
Main Authors: Andrade-Oliva, María-de-los-Angeles, Escamilla-Sánchez, Juan, Debray-García, Yazmín, Morales-Rubio, Russell A., González-Pantoja, Raúl, Uribe-Ramírez, Marisela, Amador-Muñoz, Omar, Díaz-Godoy, Raúl V., De Vizcaya-Ruiz, Andrea, Arias-Montaño, José-Antonio
Format: Article
Language:English
Subjects:
Affinity
D2 receptor
Depolarization
Dopamine
Dopamine D2 receptors
Exposure
Fine particles
Forskolin
Health risks
Mental disorders
Movement disorders
Neostriatum
Nerve endings
Neurodegenerative diseases
Neurotoxicity
Oxidative stress
Parkinson's disease
Pollutants
Quinpirole
Receptor density
Receptors
Schizophrenia
Signaling
Striatum
Synaptosomes
Toxicity
Ultrafine particles
Ultrafines
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Summary:•Fine (FP) and ultrafine (UFP) particles inhibit dopamine uptake and enhance release by striatal synaptosomes.•FP and UFP increase the affinity of D2 receptors (D2Rs) for dopamine.•FP and UFP increase the potency of D2R agonists to inhibit cAMP formation.•FP and UFP particles can directly affect dopaminergic transmission. The exposure to environmental pollutants, such as fine and ultrafine particles (FP and UFP), has been associated with increased risk for Parkinson’s disease, depression and schizophrenia, disorders related to altered dopaminergic transmission. The striatum, a neuronal nucleus with extensive dopaminergic afferents, is a target site for particle toxicity, which results in oxidative stress, inflammation, astrocyte activation and modifications in dopamine content and D2 receptor (D2R) density. In this study we assessed the in vitro effect of the exposure to FP and UFP on dopaminergic transmission, by evaluating [3H]-dopamine uptake and release by rat striatal isolated nerve terminals (synaptosomes), as well as modifications in the affinity and signaling of native and cloned D2Rs. FP and UFP collected from the air of Mexico City inhibited [3H]-dopamine uptake and increased depolarization-evoked [3H]-dopamine release in striatal synaptosomes. FP and UFP also enhanced D2R affinity for dopamine in membranes from either rat striatum or CHO-K1 cells transfected with the long isoform of the human D2R (hD2LR)2LR). In CHO-K1-hD2L In CHO-K1-hD2LR cells or striatal slices, FP and UFP increased the potency of dopamine or the D2R agonist quinpirole, respectively, to inhibit forskolin-induced cAMP formation. The effects were concentration-dependent, with UFP being more potent than FP. These results indicate that FP and UFP directly affect dopaminergic transmission.
ISSN:1382-6689
1872-7077
DOI:10.1016/j.etap.2020.103484