Beta-adrenergic receptors, from their discovery and characterization through their manipulation to beneficial clinical application.

ß-Adrenergic receptors (ß-AR) are central to the overall regulation of cardiac function. From the first proposed receptor/transmitter concept to the latest clinical ß-blocker trials ß-AR have been shown to play an important role in cardiac disease and heart failure in particular. This study provides a historical perspective, reviews the latest discoveries and beliefs, and discusses the current clinical practices of ß-AR and their modulation with their associated guanine-nucleotide regulatory protein/adenylylcyclasesignal transduction pathways.

A decade of discoveries in cardiac biology.

The heart is the first organ to form in the embryo, and all subsequent events in the life of the organism depend on its function. Inherited mutations in cardiac regulatory genes give rise to congenital heart disease, the most common form of human birth defects, and abnormalities of the adult heart represent the most prevalent cause of morbidity and mortality in the industrialized world. The past decade has marked a transition from physiological and functional studies of the heart toward a deeper understanding of cardiac function (and dysfunction) at genetic and molecular levels. These discoveries have provided new therapeutic approaches for prevention and palliation of cardiac disease and have raised new questions, challenges and opportunities for the future.

The superfamily of heptahelical receptors.

Despite a growing appreciation of functional analogies between visual and hormonal signalling systems in the early 1980s, the discovery of the close structural relationship between rhodopsin and the beta2-adrenergic receptor, and of the existence of a larger 'superfamily' of such receptors, came as a total surprise. Here I provide a personal perspective on events leading up to and flowing from this exciting discovery that opened up a vast field of research.