The binding of signaling molecules to receptors is reversible. As the external concentration of signaling molecules falls, fewer receptors are bound at any given moment, and the unbound receptors revert to their inactive form. The cellular response occurs only when the concentration of receptors with bound signaling molecules is above a certain threshold. When the number of active receptors falls below that threshold, the cellular response ceases. Then, by a variety of means, the relay molecules return to their inactive forms: The GTPase activity intrinsic to a G protein hydrolyzes its bound GTP; the enzyme phosphodiesterase converts cAMP to AMP; protein phosphatases inactivate phosphorylated kinases and other proteins; and so forth.
