Characterization and functional divergence of the α1-adrenoceptor gene family: insights from rainbow trout (Oncorhynchus mykiss)

Abstract

Presently, three α1-adrenoceptor (AR) types are recognized in vertebrates: α1A-, α1B-, and α1D-ARs. These α1-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 α1-AR gene family, we sequenced these α1-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 α1-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 α1-ARs in fish is more complex than previously thought. Our integrated analysis of the α1-AR gene family suggests that these receptors evolved these distinct features very early within vertebrates.