Mechanistic model of G-protein signal transduction. Determinants of efficacy and effect of precoupled receptors.

摘要: Abstract Tissue-specific characteristics (e.g. receptor number) and agonist-specific agonist binding kinetics) play roles in determining cellular response. The that these are quantified by models of signal transduction. We examined transduction through G-protein-linked receptors, using a model based on the collision coupling but including interconverting states precoupling receptors with G-proteins prior to addition agonist. Reaction diffusion molecules within plasma membrane were simulated Monte Carlo techniques. G-protein activation produced our was compared model. quantitatively how parameters characteristic tissue determine midpoint maximal response dose-response curve. Activation precoupled can produce significantly higher rates than does coupling. Tissue have qualitatively similar effects distinct for two models. Using standard experimental techniques, it may be possible exploit differences mechanism specific cell system. A quantitative comparison predictions published data β-adrenergic system (Stickle D Barber R, Mole Pharmacol40: 276–288, 1991) also is presented.