Morphological and pharmacological studies of the parietal cells of the stomach in the dog during periods of maximal acid output and after the gastric secretory inhibitor UK-9040.

UK-9040, a derivative of the antihistamine triprolidine, is a potent gastric secretory inhibitor. Given orally to dogs it reduced gastric acid, pepsin and volume output in response to food, insulin, histamine, N-methyl histamine, and pentagastrin. Doses of 6-36 mg/kg administered orally four to five hours before the secretagogues produced a dose-dependant and up to 100% inhibition in the outputs of innervated gastric fistula and denervated Heidenhain pouch. Inhibition was still present 24 hours after administration of UK-9040 but was absent at 48 hours. Blood pressure and pulse rate were not affected. Studies with the electron microscope revealed that the normal ultrastructural responses to gastric secretory stimulation were arrested. UK-9040 showed no cumulative effect, tolerance did not occur, and after withdrawal of the drug the physiological and morphological gastric responses of the parietal cells rapidly returned to normal.