Hormone receptor-coupling factor-adenylate cyclase interaction: theoretical considerations.
The steady-state response properties of two current models for receptor/nucleotide coupling protein/adenylate cyclase systems are examined by computer modeling techniques. In the model of Levitzki (Trends Pharmac. Sci., May, 1982, pp. 203-208), a ligand may give rise to full or partial agonist behavior only. In the model of Stadel, DeLean, and Lefkowitz (1982) configurations of the rate constants can be found which lead not only to full or partial agonist behavior, but also to varying degrees of inhibition at sufficiently high concentrations of ligand, as observed experimentally in a variety of adenylate cyclase systems. In the latter model, it is also possible to find configurations of the rate constants for which addition of a ligand will lead to inhibition of adenylate cyclase activity. The nature of partial agonism and reasons as to why it may be expected to occur for a wide variety of ligands are discussed.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D019204:GTP-Binding Proteins / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008954:Models, Biological; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D008024:Ligands; D011943:Receptors, Adrenergic, beta; D011956:Receptors, Cell Surface; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases