COMPARISON OF EFFECTS OF FAMOTIDINE ON VAGALLY AND FIELD-ELECTRICALLY STIMULATED ACID-SECRETION IN THE ISOLATED MOUSE WHOLE STOMACH

Effects of famotidine on neuronally evoked acid secretion were investigated by means of vagal (at the lower esophagus level) and field-electrical stimulation (around the stomach) in the isolated mouse whole stomach preparation. Each of the electrical stimulations caused a frequency-dependent (1 to 20 Hz) increase in acid output, and the secretory response was abolished by tetrodotoxin or atropine. In the case of field stimulation, the acid secretion was not completely inhibited by hexamethonium. When 10 Hz frequency was applied with either vagal or field-electrical stimulation, the acid secretion was only partly inhibited by famotidine at doses of up to 30 mu M. In contrast, the acid response to 2 Hz stimulation was almost completely inhibited by 1 mu M famotidine. In the presence of neostigmine (30 nM), the 2 Hz vagally stimulated acid secretion became partly resistant to the effect of famotidine (10 mu M). These results suggest that both vagally and field-electrically stimulated acid secretions have essentially the same characteristics and that the secretory mechanism through histamine release is exclusively dominant with weak stimulation, while the cholinergic mechanism on parietal cells is sufficient for reaching the maximal secretory response with strong stimulation.