Modelling the consequencesof receptor-G-protein promiscuity

Many G-protein-coupled receptors interact with more than one type of G protein, giving rise to extreme variability in the effects of receptor activation, depending on, for example, receptor density and desensitization, efficacy of agonists, and availability of specific G proteins. This leads to errors in interpretation of data. To facilitate understanding the consequences of receptor-G-protein promiscuity, we use two simplified models to simulate such consequences. Applied to the regulation of adenylyl cyclase and phosphoinositidase, the models predict seemingly paradoxical situations and explain some phenomena that, at first sight, might seem to require the induction of agonist-specific (G-protein-selective) receptor conformations.