Many extracellular signals acting via GPCRs affect the activity of the enzyme adenylyl cyclase and thus alter the intracellular concentration of the second messenger molecule cyclic AMP.

Most commonly, the activated G protein α subunit switches on the adenylyl cyclase, causing a dramatic and sudden increase in the synthesis of cyclic AMP from ATP.

To help terminate the signal, a second enzyme, called cyclic AMP phosphodiesterase, rapidly converts cyclic AMP to ordinary AMP. Cyclic AMP phosphodiesterase is continuously active inside the cell. Because it eliminates cyclic AMP so quickly, the cytosolic concentration of this second messenger can change rapidly in response to extracellular signals, rising or falling tenfold in a matter of seconds.

Cyclic AMP is water-soluble, so it can, in some cases, carry the signal throughout the cell, traveling from the site on the membrane where it is synthesized to interact with proteins located in the cytosol, in the nucleus, or on other organelles. One way that caffeine acts as a stimulant is by inhibiting this phosphodiesterase in the nervous system, blocking cyclic AMP degradation and thereby keeping the concentration of this second messenger high.