Heterogeneity of alpha-Adrenergic Responsiveness in Vascular Smooth Muscle: Role of Receptor Subtypes and Receptor Reserve

The existence of receptor subtypes (including those of alpha- and beta-adrenergic receptors) is usually postulated when faced with results obtained with novel agonists or antagonists that cannot be explained within the existing framework of receptor classification (Ahlquist, 1980; McGrath, 1982). Once receptor subclassification has been proposed on a functional basis, attempts are then made to confirm the existence of the different subtypes by receptor binding studies or receptor isolation techniques. For example, 10 yr. after the existence of alpha-1 adrenergic receptors was suggested by functional studies, these receptor sites are thought to be macromolecular structures (molecular weight, 160,000 daltons) that traverse the plasma membrane and extend above the lipid surface (Venter et al., 1984a,b). Although we are close to understanding the molecular structure and biological environment of the alpha-1 adrenergic receptors, their relative importance in vascular smooth muscle, their relationship with the other subtype(s) of alpha-adrenergic receptors, and the basis for differential modulation of the réponses to alpha-1 and alpha-2 adrenergic receptor activation are unclear. This chapter attempts to clarify these issues. These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.