The β-Adrenergic Receptor: Ligand Binding Studies Illuminate the Mechanism of Receptor-Adenylate Cyclase Coupling
This chapter relates the study of adrenergic receptors to the regulation of adenylate cyclase activity. The ubiquitous nature of the adrenergic responses has made these systems prototypes or models for the study of receptor-effector coupling in general. Progress is being made in the elucidation of the molecular mechanisms of transmembrane signaling via adrenergic receptors. The focus is primarily on studies of the β-adrenergic receptor-adenylate cyclase complex. Smooth muscle relaxation, inotropic and chronotropic regulation in the heart, and metabolic effects such as lipolysis are mediated through β-adrenergic receptors. β- Adrenergic responses are inhibited by a different set of drugs, which has little affinity for the α-receptors, such as propranolol, alprenolol, and pindolol. The characteristics of high potency and biological specificity make antagonist compounds particularly useful in the classification of adrenergic responses and in the direct study of adrenergic receptors. β-Adrenergic responses are directly linked to the activation of adenylate cyclase in the plasma membranes of target cells, suggesting that cyclic AMP (CAMP) mediates the regulatory effects of β-adrenergic agonists. The chapter discusses how understanding of receptor-cyclase coupling distilled from the investigations of the stimulatory β-adrenergic receptor-adenylate cyclase system may be applicable in understanding inhibition of adenylate cyclase activity, as mediated, for example, by α2- adrenergic receptors. © 1983, Academic Press Inc.
