Both Ligand- and Cell-Specific Parameters Control Ligand Agonism in a Kinetic Model of G Protein–Coupled Receptor Signaling
Figure 7
Protean Agonism in the β2-Adrenergic Receptor System
(A) Dichloroisoproterenol (DCI) effect on adenylyl cyclase activity in Sf9 cells. DCI was found to be both a partial agonist (•) and an inverse agonist (○) in this study. Data replotted from Chidiac et al. (1996).
(B) Simulations of DCI activation of GαGTP. Protean agonism properties of DCI caused by 5-fold difference in G protein concentration.
(C) After desensitizing treatment with isopreterenol, DCI was found to inhibit adenylyl cyclase activity in membranes where previously positive agonism was seen (•). This treatment further decreased activity of adenylyl cyclase in membranes where inverse agonism was observed (○). Data replotted from Chidiac et al. (1996).
(D) Desensitization treatment by isopreterenol is simulated by decreasing G protein (Gtotal) by 50%. Parameter values are equal to those listed in Figure 4 except when otherwise noted. Rtotal = 4,000/cell, α = 0.5, δ = 5. Simulated dose response curves (B,D) measuring the percent accumulation of GαGTP (%Accum) were calculated according to Equation 2 as described in Methods.