GPCR signal transduction pathways that use adenylyl cyclase as an effector protein and cAMP as a second messenger are found in most mammalian cells, where they regulate cellular functions as diverse as metabolism of fats and sugars, synthesis and secretion of hormones, and muscle contraction. These pathways follow the general GPCR mechanism outlined in Figure 15-14: ligand binding to the receptor activates a coupled heterotrimeric G protein, termed G_αs, that activates an effector protein—in this case, adenylyl cyclase, which synthesizes the diffusible second messenger cAMP from ATP (Figure 15-23). The cAMP, in turn, activates a cAMP-dependent protein kinase that phosphorylates specific target proteins. In mammals, more than 30 different GPCRs activate G_αs and adenylyl cyclase; most cell types express one or more such GPCRs. As detailed in Classic Experiment 15-1, early studies of the mechanism of activation of adenylyl cyclase led to the discovery of the role of the first GTP-binding protein in receptor signaling.

To explore this GPCR/cAMP pathway, we focus on the first such pathway discovered: the hormone-stimulated generation of glucose-1-phosphate from glycogen, a storage polymer of glucose (Figure 15-24). The breakdown of glycogen (glycogenolysis), which occurs in muscle and liver cells in response to hormones such as epinephrine and glucagon, is a principal way in which glucose is made available to cells in need of energy. This example shows how activation of a GPCR can stimulate or inhibit several intracellular enzymes, all coordinated to carry out a physiologically important task: glycogen metabolism.