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

Abstract

Background:

Three different α₂-adrenoceptor (α₂-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 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 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 α₂-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.