Characterization and functional divergence of the alpha 1-adrenoceptor gene family: insights from rainbow trout (Oncorhynchus mykiss)

Presently, three alpha(1)-adrenoceptor (AR) types are recognized in vertebrates: alpha(1A)-, alpha(1B)-, and alpha(1D)-ARs. These alpha(1)-subtypes have distinct pharmacology and molecular profiles, play crucial roles in metabolic and vascular control, and are the targets for numerous pharmaceuticals, especially those affecting blood pressure and vascular resistance. To better understand the functional divergence within the alpha(1)-AR gene family, we sequenced these alpha(1)-AR paralogs in the rainbow trout and performed an extensive phylogenetic analysis. We show that these AR genes evolved by duplication events just before the origin of the jawed vertebrates. Our computational analyses suggest that the differences between the three alpha(1)-AR subtypes may affect their tissue specificity, ligand specificity, and possibly signal transduction processes and desensitization. We also show that, within each subtype, differences exist between fish and mammalian receptors, both at the transcriptional and at the physiological level. These differences, however, suggest that the role of alpha(1)-ARs in fish is more complex than previously thought. Our integrated analysis of the alpha(1)-AR gene family suggests that these receptors evolved these distinct features very early within vertebrates.