The beta-adrenergic receptor. Configuration, regulation, mechanism of action

Much has been learned in the 25 years since a beta-blocking drug was first administered to humans. The beta-adrenergic receptor has been divided into two general subtypes, and these have been purified to homogeneity. The beta 2-receptor gene has been cloned, and the primary structure of the beta 2 receptor has been deduced. Additionally, important details of the receptor-adenylate cyclase complex have been elucidated. Another general category of information relates to the unique features of the myocardial beta-adrenergic receptor population. These include (1) a relatively high proportion of beta 2 receptors and coupling of these receptors to muscle contraction; (2) the apparent lack of spare receptors; (3) selective down-regulation of the beta 1-receptor population in heart failure, with preservation of the beta 2 and alpha 1 populations; and (4) mediation of the most powerful inotropic stimulus that can be delivered by a receptor-coupled pathway. In the next 25 years, investigations will emphasize the use of molecular biologic techniques to discover crucial information about the control of beta-receptor structure and function. From this research will come both new pharmacologic agents and new applications of currently available agents.