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

Abstract

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 (hD_2LR)2LR). In CHO-K1-hD2L In CHO-K1-hD_2LR 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.

Keywords: D(2) receptor; Dopamine; Fine particles; Signaling; Striatum; Ultrafine particles.