The effects of some adrenoceptor agonists and antagonists which have been reported to affect histamine formation in leucocytes (Assem & Feigenbaum, 1972) have been investigated on gastric secretion in conscious dogs with Heidenhain pouches. Submaximal secretion in response to pentagastrin was enhanced by propranolol (0.1–1.0 mg/kg i.v.) and phenylephrine (1.0 μg kg−1 min−1 i.v. for 20 min), which increase histamine formation, and was decreased by phentolamine (2 mg/kg i.v.) and isoprenaline (0.05–0.2 μg kg−1 min−1 i.v. for 30 min), which decrease histamine formation. Practolol (2 mg/kg i.v.), which has no effect on histamine formation, had no effect on secretion. Acid secretion in response to histamine was either unaffected or affected in the opposite direction by these drugs. The effects of the drugs on pentagastrin‐induced secretion were not secondary to changes in mucosal blood flow (radioactive aniline clearance). The results are consistent with the hypothesis that acid secretion in response to pentagastrin involves the formation of endogenous histamine.

SUMMARYBackground: No standard methods exist for determining the onset of action of gastric antisecretory agents in human subjects. Methods: Intragastric pH was measured when placebo, ranitidine 150 mg, ranitidine 75 mg or famotidine 10 mg were administered 30 min after the end of a meal. Results: When the onset of action was defined as the earliest time that mean gastric pH with active treatment was statistically significantly higher (P < 0.05) than the corresponding placebo value, the onsets of action of ranitidine 75 mg and 150 mg were 55 min, and of

Previous work has shown that the duodenal ulcer population can be defined by a lower ratio between gastric mucosal blood flow and acid secretion (during pentagastrin stimulation) than is found in normal subjects. The results of the present investigation have shown that the ratio is restored to normality by highly selective vagotomy. This suggests that increased tonic activity of the vagus on the parietal cell is one of the important disorders in duodenal ulceration.

Gastric mucosal blood flow (neutral red clearance, NRC) and acid secretion were measured before and after highly selective vagotomy (HSV). Eleven patients with duodenal ulcer were studied before and 12–21 days after HSV. Eight volunteers were also studied using the histamine‐H2‐receptor antagonists cimetidine and ranitidine. Basal secretion was collected for 40–50 minutes and pentagastrin was given in increasing doses each for 40 minutes. Data were analyzed using Wilcoxon's signed‐ranks test for paired samples and an analysis of covariance. Basal NRC was similar both for patients and for volunteers and was unaffected by HSV. There was a linear correlation between NRC and acid output. The patients with duodenal ulcer had a lower ratio of NRC to acid during pentagastrin stimulation than was found in normal subjects, but the regression line after HSV was comparable to that found for the volunteers. Although stimulated acid output was reduced by HSV, NRC was significantly higher after HSV than before. The 2 histamine‐H2‐receptor antagonists reduced both NRC and acid to a similar extent, and this could not be overcome by increasing the dose of pentagastrin. These results indicate that mucosal blood flow and acid secretion may not be unconditionally linked, although a linear relationship was always found. HSV produces an effect on blood flow that is not linked to the reduction in acid output.

Histamine has been investigated for its effect on gastric acid secretion and mucosal blood flow in man. Dose-response curves were constructed and analysed in the presence of H1- and H2-antagonists. Mepyramine had no effect on acid secretion or mucosal blood flow. Cimetidine reduced acid secretion but had no effect on blood flow. This suggests that the vasculature is less sensitive to cimetidine than the parietal cell.