α1-Adrenoreceptor in human hippocampus: Binding and receptor subtype mRNA expression

Abstract

α₁-Adrenoreceptors (AR), of which three subtypes exist (α_1A-, α_1B- and α_1D-AR) are G-protein-coupled receptors that mediate the actions of norepinephrine and epinephrine both peripherally and centrally. In the CNS, α₁-ARs are found in the hippocampus where animal studies have shown the ability of α₁-AR agents to modulate long-term potentiation and memory; however, the precise distribution of α₁-AR expression and its subtypes in the human brain is unknown making functional comparisons difficult. In the human hippocampus, ³H-prazosin (α₁-AR antagonist) labels only the dentate gyrus (molecular, granule and polymorphic layers) and the stratum lucidum of the CA3 homogenously. Human α_1A-AR mRNA in the hippocampus is observed only in the dentate gyrus granule cell layer, while α_1D-AR mRNA expression is observed only in the pyramidal cell layers of CA1, CA2 and CA3, regions where ³H-prazosin did not bind. α_1B-AR mRNA is not expressed at detectable levels in the human hippocampus. These results confirm a difference in hippocampal α₁-AR localization between rat and humans and further describe a difference in the localization of the α_1A- and α_1D-AR mRNA subtype between rats and humans.