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This study was designed to determine the role of cholecystokinin (CCK) in postprandial motility pattern of the duodenum and gallbladder (GB) in conscious dogs provided with chronic duodenal electrodes for recording of myoelectric activity and GB fistulas for measurement of intraluminal pressure and volume of GB and to calculate the GB motility index (MI) and GB emptying rate. During naturally occuring activity front (phase III MMC) in the duodenum there was significant increase in the MI of GB accompanied by about 20-30% reduction in the GB volume. These changes in duodenal and GB motility pattern could be duplicated by i. v. motilin. Feeding abolished the appearence of spontaneous activity front in the duodenum and greatly increased motility of GB while reducing its volume. Administration of CCK receptor antagonists in fed dogs failed to affect the motility changes induced by meal in the duodenum but abolished these of the GB. Vagal cholinergic stimulation with insulin, 2DG or urecholine caused similar effects to that induced by food i. e. increased duodenal spike activity, abolished phase III of the MMC, decreased GB volume and increased GB motility. Pretreatment with CCK antagonists did not affect significantly duodenal spike activity or GB motility but significantly increased the GB volume. Atropine 125 µg/kg) blocked almost completely spontaneous activity front in the duodenum and accompanying alterations in the motiliti and volume of GB. We conclude that CCK contributes to the MMC related alterations in the GB motor activity and is essential in cholinergic stimulation induced of the GB emtying but not in vagally induced duodenal and GB motility.
This study was designed to assess the gastric secretory effects of ebrotidine, a novel H₂ receptor antagonist, in humans. Three groups (A, В and C) of male subjects with normal gastric mucosa were used. Group A (6 subjects) was used to determine the dose-dependency of gastric inhibitory effect of ebrotidine on basal and pentagastrin- induced maximal acid output. Group В (8 subjects) was employed to examine the duration of the inhibitory effect of ebrotidine on basal and pentagastrin-induced acid secretion. In group C (6 subjects), the 24 h pH-metry was assessed using intraluminal pH-electrode placed in the gastric corpus and connected to a portable recording unit. Single oral dose of ebrotidine (200, 400 or 800 mg) caused a dose- dependent reduction in basal and pentagastrin-induced acid secretion that at a dose of 800 mg amounted to about 89% and 93%, respectively. This inhibition was still observed after 6h and averaged 72% and 50%, respectively. After 12 and 24 h upon the drug intake, both basal and pentagastrin-induced acid secretion returned to the control values. Single oral dose of ebrotidine (800 mg) caused a significant reduction in circadian acidity and resulted in a marked and significant reduction of intragastric acidity for about 6 h upon the administration. This inhibition was accompanied by a transient increase in basal and postprandial gastrin levels. We conclude that ebrotidine is highly effective inhibitor of basal, pentagastrin-induced and circadian gastric acid secretion in humans.
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