Acta Pharmacologica Sinica 2005 November; 26 (11): 1281-1287; doi: 10.1111/j.1745-7254.2005.00224.x

α₁-Adrenergic receptors (AR) play an important role in the regulation of physiological responses mediated by norepinephrine and epinephrine, particularly in the cardiovascular system. The three cloned α₁-AR subtypes (α_1A, α_1B, and α_1D) are G protein-coupled receptors that signal through the G_q/11 signaling pathway, each showing distinct pharmacological properties and tissue distributions. However, due to the lack of highly subtype-selective drugs, the functional roles of individual subtypes are still not clear. Development of new subtype-specific drugs will greatly facilitate the identification of the functions of each subtype. Conopeptide ρ-TIA has been found to be a new α_1B-AR selective antagonist with different modes of inhibition at α₁-AR subtypes. In addition, recent studies using genetically engineered mice have shed some light on α₁-AR functions in vivo, especially in the cardiovascular system and brain. Several proteins have been shown to interact directly with particular α₁-AR, and may be important in regulating receptor function. Receptor heterodimerization has been shown to be important for cell surface expression, signaling and internalization. These new observations are likely to help elucidate the functional roles of individual α₁-AR subtypes.

Keywords: alpha1-adrenergic receptor; noncompetitive drug; protein-protein interaction; dimerization; cell surface expression