Figure 1.

Simulated concentration-response curves to competitors with different intrinsic efficacies on the response to a full agonist (A) or a full inverse agonist (B). (A) Occupancy of the receptor by the full inverse agonist produces 175 units of response. Competition with a ligand of lower intrinsic efficacy reduces the response of the full agonist such that when occupancy of the receptor has been fully replaced by the competitor, the response remaining is due to the competitor and is dependent on the maximal response produced by the competitor. (B) Occupancy of the receptor by the full inverse agonist reduces the basal response (arbitrarily denoted here as 100 units) to 30 units. As a result of competition produced by ligands with higher intrinsic efficacy, the response of the full inverse agonist is reduced to become commensurate to the efficacy of the competitor. Note, the response elicited by the full inverse agonist is not zero, as there remains constitutive activity of signaling molecules (e.g., G proteins) and effectors in the system capable of producing 30 units of response in the absence of constitutive receptor activity.