MOLECULAR MIXTURE-MODELS BASED ON COMPETITIVE AND NONCOMPETITIVE AGONISM

Agonists in mixtures may bind to a common receptor or to independent receptors. Signal generation may also depend on a transducer, such as a G protein. Interactions among agonists, receptors and transducers lead to changes in the activity of effectors, such as adenylyl cyclase, resulting in signals which affect behavior. In this paper, six molecular mixture models are presented, four of which are derived for the first time. These models distinguish between two important properties of chemicals as they interact with receptor cells and transducers: their affinity in binding to receptors and their efficacy in producing a particular effect, such as taste perception. Several generalizations can be drawn from these new models: (i) if a common receptor for two substances exists and if simple binding to the receptor occurs, there will be a linear relationship between the components of mixtures which have equal perceptual, or other, effects, even following an additional transduction step prior to perception; (ii) if co-operative binding to a common receptor occurs, the relationship between mixture components will be non-linear, and (iii) if simple binding to independent receptors occurs, the relationship between mixture compounds may be non-linear (for example, a synergistic effect), and similar to (ii). These models were evaluated using the data of De Graaf and Frijters (1986) on the perceived sweetness of binary mixtures of glucose and fructose. The results of this analysis revealed that if a common receptor occurs for these two compounds, co-operative binding must also exist. If simple binding occurs, then independent receptors and the participation of a third binding entity are required to model the data.