We’ve seen that receptors such as the β-adrenergic receptor are low-abundance proteins, typically present in only a few hundred or thousand copies per cell. Yet the cellular responses induced by a hormone such as epinephrine can require production of large numbers of cAMP and activated enzyme molecules per cell. As an example, following activation of G_αs-coupled receptors, the intracellular concentration of cAMP rises to about 10⁻⁶ M. In a typical cell, that is roughly a cube about 15 µm on a side; this concentration is equivalent to 2 million molecules of cAMP per cell. Thus substantial amplification of the signal is necessary if it is to induce a significant cellular response. We have already seen how signal amplification occurs following photon absorption in rod cells. In the case of G protein–coupled hormone receptors, signal amplification is possible in part because both receptors and G proteins can diffuse rapidly in the plasma membrane. A single epinephrine-GPCR complex causes conversion of up to a hundred inactive G_αs molecules to the active form before epinephrine dissociates from the receptor. Each active G_αs·GTP, in turn, activates a single adenylyl cyclase molecule, which then catalyzes the synthesis of many cAMP molecules during the time G_αs·GTP is bound to it.

The amplification that occurs in such a signal transduction cascade depends on the number of steps in it and on the relative concentrations of the various components. In the epinephrine-induced cascade shown in Figure 15-7 and Figure 15-29, for example, blood levels of epinephrine as low as 10⁻¹⁰ M can stimulate liver glycogenolysis and release of glucose. An epinephrine stimulus of this magnitude generates an intracellular cAMP concentration of 10⁻⁶ M, an amplification of 10⁴-fold. Because three more catalytic steps precede the release of glucose, another 10⁴ amplification can occur, resulting in a 10⁸ amplification of the epinephrine signal. In striated muscle, the amplification is less dramatic because the concentrations of the three successive enzymes in the glycogenolytic cascade—PKA, GPK, and GP—are in a 1:10:240 ratio (a potential 240-fold maximal amplification).