Fig. 1.
Two-state model of GPCR activation. A receptor can exist in an inactive (R) or active (R*) form. An inactive receptor may isomerize to the active form (R*) even in the absence of an agonist, a property known as constitutive activity. Once the ligand is bound, the receptor can exist in two states, occupied (AR) or occupied and activated (AR*), the latter being the species that couples to G protein (Strange, 2000). The position of equilibrium between R and R* will depend on the isomerization constant (L), the conformational change that takes place. An inverse agonist will bind stronger to R keeping the receptor in the inactive state (form AR), whereas an agonist will bind stronger to R* pushing the equilibrium toward AR*. KA and KA/α are the equilibrium constants for agonist binding to the receptor conformations R and R*, respectively; α defines the efficacy of A.