Differential expression of two α₂-adrenergic receptor subtype mRNAs in human tissues

Genetic subtypes of α₂-adrenergic receptors (AR) may mediate distinct physiological functions, and undergo differential cell type-specific regulation. Thus, these distinct receptor subtypes are possible targets for the development of subtype-selective drugs. We have analyzed the tissue distribution of two human α₂-adrenoceptor subtype gene mRNAs, α₂-C4 and α₂-C10, in normal human fetal and adult tissues. Both receptor subtype mRNAs were abundantly expressed in fetal brain and choroid plexus. In non-neural fetal tissues, α₂-C10 mRNA was detected in spleen, kidney, adrenal gland, and skin, while α₂-C4 transcripts were observed only in kidney and skin. Most regions of the adult brain also expressed both subtypes, but with marked quantitative differences. For example, cerebral cortex contained predominantly α₂-C10 mRNA, whereas the caudate nucleus expressed mostly α₂-C4 mRNA. In adult peripheral tissues, α₂-C10 mRNA expression was most abundant in spleen and renal cortex, and expression of α₂-C4 mRNA was strongest in renal cortex and medulla. These different expression patterns provide evidence for the differential regulation of the two α₂-adrenergic receptor genes and warrant further investigation with techniques capable of improved anatomical resolution. Regional differences in receptor subtype expression may be valuable for the development of new, subtype-selective pharmacological agents with more targeted actions compared to currently used α₂-adrenoceptor agonists and antagonists.