The role of secretin in the inhibition of gastric secretion by intraduodenal acid

Abstract

SUMMARY The effect of intraduodenal acid on pentagastrin-stimulated gastric secretion has been investigated in 12 normal subjects and 23 patients with chronic duodenal ulceration. Plasma secretin levels were monitored during each test using a highly sensitive radioimmunoassay.Significant inhibition of gastric secretion occurred in the normal subjects and duodenal ulcer patients. A significant rise in plasma secretin was observed in both groups after intraduodenal acid though there was a complete lack of correlation between the magnitude of the secretin response and the degree of gastric inhibition. Ten subjects received intraduodenal acid and a subsequent intravenous infusion of exogenous secretin (0.125-0.25 units/kg over six minutes). Gastric inhibition occurred after the acid instillation but not after secretin infusion despite plasma secretin levels greatly in excess of those produced by intraduodenal acid.These results suggest that release of secretin by itself cannot explain the gastric inhibitory response to intraduodenal acid in man.The presence of acid in the duodenum is known to inhibit gastric secretion both in animals (Pincus, Friedman, Thomas, and Rehfuss, 1944;Sircus, 1958) and in man (Shay, Gershon-Cohen, and Fels, 1942;Johnston and Duthie, 1964). The mechanism of this response is, however, uncertain. The main possibilities (which may of course interact) appear to be either a vagal reflex or a humoral response particularly involving secretin. The evidence for each of these views is fully discussed elsewhere (Ward, 1974). The role of the vagus has been examined in detail and it appears likely that gastric inhibition is dependent on a vagal reflex in man (Ward, 1974). Strong claims, however, have been made that in dogs secretin is the mediator of gastric inhibition by intraduodenal acid (Johnson and Grossman, 1968) and the present study was therefore undertaken to examine the response with particular emphasis on the role of secretin. Materials and MethodsThe response to intraduodenal acid was investigated in 35 patients, 10 of whom also received an intravenous secretin infusion. There were 12 normal subjects (Orm, 2f) and 23 patients (21m, 2f) with chronic duodenal ulceration. The average age of Received for publication 10 July 1974. the normal subjects was 38 years (range 21-63) and their average weight 71 kg (range 55-83 kg). These subjects were awaiting minor inpatient surgery and all were free of gastrointestinal symptoms. The duodenal ulcer patients were awaiting gastric surgery and in all cases the pathology was confirmed subsequently at laparotomy. Their average age was 42 years (range 27-67) and their average weight 68 kg (range 52-82 kg).A duodenal inhibitory test (Ward, 1973) was carried out on each of the normal subjects and duodenal ulcer patients. The gastric stimulus was an intravenous infusion of pentagastrin at a dose rate of 6 ,g/kg/hr. Gastric samples were collected at 10-minute intervals throughout the test.Once a secretory plateau had been reached 40 ml of 0O1N hydrochloric acid ...

The interaction of secretin and stimulants of gastric acid secretion in anaesthetized cats.

“…All the published work in man and cats has employed doses of GIH secretin in excess of 1 c.u./kg or 2 c.u./kg hr which are likely to exceed the amount of secretin released during feeding (Vagne, Descos & Martin, 1969;Meyer et at. 1970;Ward & Bloom, 1974 (Braganza et al 1975a). We have shown previously that acid stimulants which produce little or no pepsin enhance the peptic response to a dose of secretin, itself below the threshold of peptic stimulation by increasing gastric mucosal blood flow (Reed & Sanders, 1971;Reed, Smy, Venables & Harris, 1973) and thus causing a 2-4-fold increase in the concentration of secretin in the peptic cell (Braganza et al 1975a).…”

“…The amount of secretin released during feeding maybe less than theequivalent ofGIH secretin 0 5 c.u./kg hr both in dog (Meyer, Way & Grossman, 1970) and in man (Ward & Bloom, 1974), a dose which initiates pancreatic secretion in the anaesthetized cat. 74 J. M. BRAGANZA, A. C. C. GIBBS AND H. T. HOWAT Experiments in which four acid stimulants were administered singly and together with Boots secretin 4 Crick-Harper-Raper u./kg hr which is equivalent to GIH secretin 1 c.u./kg hr as a pancreatic stimulant (Braganza, Howat & Kay, 1975b), provided an opportunity to examine the influence of a small dose of secretin on the acid secretion in cats.…”

Inhibition of Gastric Electrical and Mechanical Activity by Intraduodenal Agents in Pigs and the Effects of Vagotomy

“…Radioimmunoassays of circulating secretin have also suggested that the amounts released during acid stimulation were much smaller than the circulating levels apparently necessary to induce an inhibition by the exogenous hormone, at least of gastric secretion (28). On the other hand, truncal, selective and highly selective vagotomy had no effect on secretin release in man (29).…”

“…As far as the secretion is concerned, recent studies have supported the importance of a normal vagal supply in the effects of acid (26,28) and hyperosmolar agents (27). Clas sical studies of gastric motility report discordant results, some authors claiming that vagotomy suppresses the effects of acid (19,23) and others indicating that only coeliac ganglionectomy can alter acid inhibition (21).…”

Tests of Exocrine Pancreatic Function

“…Both groups agree that circulating secretin increases following intraduodenal instillation of acid. In patients with a duodenal ulcer this procedure produces only half the usual response indicating that reduction of the gastric inhibitory action of this hormone and reduced secretion of pancreatic bicarbonate may have an important role in preventing healing of such an ulcer (Ward and Bloom, 1974). Whether the failure is primary or secondary is unclear and the gastric inhibitory roles of other hormones in duodenal ulceration is not established.…”