Differential α 2A - and α 2C -adrenoceptor protein expression in presynaptic and postsynaptic density fractions of postmortem human prefrontal cortex

Background: Three different α 2 -adrenoceptor (α 2 -AR) subtypes have been described. The α 2A -AR and α 2C -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 α 2 -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 α 2A - and α 2C -ARs was measured in presynaptic membranes and postsynaptic density fractions by Western blot. Results: The results revealed that the α 2A -AR subtype is mainly located postsynaptically (95±3%) whereas the remaining 5±3% is in the presynapse. Conversely, the α 2C -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 α 2 -AR agonists and antagonists in the human prefrontal cortex. Furthermore, the present data could contribute to elucidating the therapeutic potential of selectively targeting α 2A - or α 2C -AR subtypes.