Figure 7.

Biased agonism in terms of the functional allosteric model. (A) The agonist is a modulator labelled M interacting with a receptor conduit, which also interacts with two guests labelled G_α (for a cAMP response) and β-arrestin for an association with β-arrestin. (B) Upon binding of agonist M, the affinity of the conduit changes in accordance with α_G and α_B for the particular agonist. The quality of action of the couplers also changes in accordance with β_G and β_B. (C and D) System parameters: E_m= 1; [ϕ]= 0.001 for G-protein/0.002 for β-arrestin; n = 1.6; τ= 1 for G-protein / 0.3 for β-arrestin. K_ϕ= 0.03 for both G-protein and β-arrestin. For agonist 1 (modulator M₁: K_M= 10⁻⁶ for unliganded receptor, α= 2000; β= 0.3). For agonist 2 (modulator M₂: K_M= 10–6 for unliganded receptor, α= 1000; β= 0.6). (E) Bias plot of β-arrestin response (ordinates) as a function of cAMP response (abscissa) for agonists 1 and 2 from panels C and D.