Dynamics of a metabolic system: what single-action agents reveal about acid secretion.

A simple single-state nonlinear mathematical model of an open metabolic system is shown to be an adequate representation of acid secretion in frog gastric mucosa. The parameters of the elemental model were estimated from data, and subsystems of augmented models were established for histamine, a nonconservative stimulus acting via binding to receptors, and for two inhibitors of acid secretion. The latter included metiamide, a nonconservative histamine antagonist, which affects the formation of acid by competitive binding to the histamine receptors, and nitrite, a conservative inhibitor, which affects the rate of acid translocation. For parameter estimation, two data sets were analyzed by a nonlinear least-squares procedure: a dynamic (time dependent) set consisting of individual acid secretion rate curves and an integral (time independent) set consisting of the curves of acid secreted and suppressed above or below baseline, respectively, as functions of agent exposure. Because the model is instrumental in the estimation of parameters of subsystems that are not accessible through direct observation, it can serve as a research tool in the investigation of the mechanism of gastric acid secretion under a variety of experimental conditions.