alpha(1)-adrenergic receptors: New insights and directions

The adrenergic receptors play a key role in the modulation of sympathetic n ervous system activity as well as a site of action for many therapeutic age nts. The alpha (1)-adrenergic receptor subtypes (alpha (1A)-, alpha (1B)-, alpha (1D)) are the prime mediators of smooth muscle contraction and hypert rophic growth, but their characterization in both binding and function have lagged the other adrenergic family members. Although they are derived from a related ancestral gene and all nine adrenergic receptor family members b ind the endogenous ligands, epinephrine and norepinephrine, with roughly si milar affinities, there are major differences in the mode of binding, secon d messenger utilization, and physiological effects of the alpha (1)-subtype s compared with beta -or alpha (2)-subtypes. Here, we review the recent lit erature on aspects of its binding pocket and how it differs from the beta - adrenergic receptor paradigms. We also review the signaling components and aspects of its function and provide new insights into its roles in smooth m uscle, growth, neurological, and cardiovascular function.