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  • Title: Differential α2A- and α2C-adrenoceptor protein expression in presynaptic and postsynaptic density fractions of postmortem human prefrontal cortex.
    Author: Erdozain AM, Brocos-Mosquera I, Gabilondo AM, Meana JJ, Callado LF.
    Journal: J Psychopharmacol; 2019 Feb; 33(2):244-249. PubMed ID: 30255728.
    Abstract:
    BACKGROUND: Three different α2-adrenoceptor (α2-AR) subtypes have been described. The α2A-AR and α2C-AR subtypes are highly expressed in the human prefrontal cortex, where they modulate neurotransmission. However, due to the lack of subtype-selective ligands, the physiological relevance of both subtypes has not been fully resolved. AIMS: In this context, the aim of the present study was to characterize the protein expression of both α2-AR subtypes, in different synaptic fractions of postmortem human prefrontal cortex. METHODS: A subcellular fractionation of the samples was performed and the protein expression of α2A- and α2C-ARs was measured in presynaptic membranes and postsynaptic density fractions by Western blot. RESULTS: The results revealed that the α2A-AR subtype is mainly located postsynaptically (95±3%) whereas the remaining 5±3% is in the presynapse. Conversely, the α2C-AR subtype showed a similar distribution between pre- and postsynaptic membranes, with a slightly higher percentage present in the presynapse (60±2% vs. 40±2%). CONCLUSIONS: These findings could explain some contradictory effects reported for α2-AR agonists and antagonists in the human prefrontal cortex. Furthermore, the present data could contribute to elucidating the therapeutic potential of selectively targeting α2A- or α2C-AR subtypes.
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