Histamine: the sole mediator of pentagastrin-stimulated acid secretion

Isolated frog gastric mucosa was used to study the effect of pentagastrin on histamine release and acid secretion. The release of histamine precedes that of acid secretion. The delay time and time of peak acid secretion occur later than during histamine stimulation. Short exposure (pulse) results in transient increases in both acid secretion and histamine release rates, while longer exposure (step) results in prolonged increases in both variables. Dose-response curves for pentagastrin pulses show that both the total amount of histamine released and the total amount of acid secreted are saturable processes, paralleling each other. Thus, the total amount of acid secreted is a function of histamine (released) exposure (M min-1) in the extracellular space. Repeated exposure will give multiple responses only if the time elapsed between the stimuli is long enough. The magnitude of the responses depends on the length of time intervals between the stimuli and the concentration of the stimuli. Simultaneously administered pulses of histamine and pentagastrin result in merely additive amount of acid being secreted. From these observations I conclude that pentagastrin-induced acid secretion can be understood solely in terms of its effect on histamine release and that depletion of histamine stores is responsible for the observed refractoriness.