Summary and Future Endeavors

The first half of the 20th century saw the development of the concept of a receptor and the isolation of the first hormone. The last half of the 20th century revealed that there are many subtypes of the adrenergic receptors with different pharmacological properties, and that they are coupled to different G proteins and signal transduction mechanisms. We then basically determined how the ligands bind to the receptor, how G proteins become activated, and how G proteins can selectively couple to receptors through interactions with the intracellular loops of the receptor. We also determined which tissues contain the different subtypes and some of the physiological processes that are regulated by the receptors. The century ended with the cloning of the receptors and the application of basic molecular biological techniques to discern the roles of the individual subtypes. Although much information was garnered in cell lines, there remained a noticeable lack of information in integrated systems and whole animal physiology.