Implications of Cross Inhibitory Interactions of Potential Mediators of Hormone and Neurotransmitter Action

• Published in: Proceedings of the National Academy of Sciences - PNAS 1976-09, Vol.73 (9), p.2982-2986
• Main Authors: Van Cauter, Eve, Hardman, Joel G., Dumont, Jacques E.
• Format: Article
• Language: English
• Subjects: Agonists; Calcium; Calcium - metabolism; Cyclic AMP - metabolism; Cyclic GMP - metabolism; Cyclic nucleotides; Extrema; Hormones; Hormones - metabolism; Induced substructures; Kinetics; Modeling; Models, Biological; Neurotransmitter Agents - metabolism; Receptors; Receptors, Cell Surface - metabolism; Receptors, Neurotransmitter - metabolism; Simulations
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.73.9.2982

Mediators of hormone and neurotransmitter action may exert negative control on the accumulation of one another (adenosine 3′:5′-cyclic monophosphate vs calcium or guanosine 3′:5′-cyclic monophosphate, or conversely). A model in which one agonist stimulates the formation of two mediators which inhibit each other's accumulation has been simulated. Three types of agonist-receptor interaction, five mechanisms of inhibition, and three types of basal activity have been considered which lead to a set of 45 descriptions of the general cross inhibition model. For these submodels, patterns of the relation of agonist to mediator concentrations at steady state conditions have been defined. Some patterns are complex with mediator curves exhibiting extrema, one a maximum and the other a minimum. The complexity of the pattern depends on the submodel and on the degree of asymmetry between the parameters of each of the mediator pathways (e.g., affinities for the agonist, strength of the inhibitions, etc.). This simple model can thus account for complex experimental results without requiring the postulation of elaborate molecular models of agonist-receptor interaction. The simulations presented emphasize the necessity of investigating a wide range of agonist concentrations.