Action of gastrin on the lower oesophageal sphincter in man

Abstract

suMMARY Both hog gastrin and synthetic gastrin stimulate the cardiac sphincter to increase tone and augment the resistance to reflux. Endogenous gastrin has a similar effect, and gastrin also stimulates the secretion of acid which has also been found to increase the resistance of the sphincter, but the effect of gastrin appears to be independent of the secretory stimulus.Now that the role of gastrin in the control of gastric acid secretion has become clearer, attention has turned to the subsidiary action of this hormone on the smooth muscle of the gastrointestinal tract. Early studies by Blair, Harper, Lake, Reed, and Scratcherd (1961) showed that an extract of antral mucosa produced a marked pressor response in the stomach and upper small intestine of anaesthetized cats. Similar results were later reported by Gregory and Tracy (1964) using an extract of hog antral mucosa to produce stimulation of intestinal motility in dogs.In an earlier study (Giles, Humphries, Mason, and Clark, 1968) we found that the intraluminal pressure of the cardiac sphincter increased when the gastric aspect of the sphincter mucosa was perfused with acid. This suggested a physiological response to gastric secretion such as after eating, and perhaps designed to increase the barrier pressure preventing gastrooesophageal reflux. Following this hypothesis it seemed reasonable to examine whether circulating gastrin, induced during eating, might have a similar effect.In the experiments to be described, the pressures exerted by the lower oesophageal sphincter have been measured before and after the injection of hog gastrins I and II in varying doses, and also after injection of synthetic gastrin (ICI 50,123). The effect of release of endogenous gastrin can be studied in man using the technique of meat extract stimulation (Giles and Clark, 1967; Giles, Buchan, and Clark, 1967). This technique has been adopted to study the effect on the cardiac sphincter in an attempt to ascertain the events likely to occur during digestion. MATERIALS AND METHODSThe methods used to measure the sphincteric pressures in these experiments were similar to those used previously (Giles et al, 1968) and measurements were made of the mean gastric pressure, maximum sphincteric pressure, and the oesophageal pressures, all calculated from the end expiratory measurements. After the sphincteric profile had been determined under resting control conditions, an injection of gastrin was given slowly intravenously and the sphincter profile was repeated after 15 minutes. The gastrin (Leo Labs) was given in a bodyweight dose which carried from 0.005 units to 1.0 units/kg.In five subjects a continuous infusion of pentagastrin (ICI 50,123) was given at a rate of 0-06 tg/kg/hr and sphincter profiles were obtained in the usual way after five and again after 25 minutes of infusion. In a further three subjects, pressure tracings were made before and 15

The Hormonal Regulation of Pyloric Sphincter Function

“…The lower esophageal sphincter contracts in response to gastrin (12)(13)(14) whereas both the ileocecal (15) and choledochal sphincters (16) (25) and suggested that contaminants present in the GIH Research Unit preparation of cholecystokinin were not solely responsible for the observed response (26)(27)(28).…”

“…The most likely mechanism by which the pylorus serves this protective function would be the release of the duodenal hormones, secretin and cholecystokinin, in response to acidification. This would be analogous to the role of gastrin in maintaining lower esophageal sphincter competence (12)(13)(14). However, other hormonal or neural pathways can not be excluded.…”

“…It has been presumed to be hormonal because the substances which were instilled into the duodenum are known to release both secretin and cholecystokinin (4)(5)(6)(7)(8)(9)(10)(11). In addition, a precedent for hormonal regulation of other gastrointestinal sphincters has been established (12)(13)(14)(15)(16). The purpose of this study is: (a) to utilize pyloric circular muscle, in vitro, to characterize the interaction of the gastrointestinal hormones on the pyloric sphincter; and (b) to relate these observations on pyloric muscle, in vitro, to studies carried out in man, in vivo.…”

Hormonal regulation of human lower esophageal sphincter competence: interaction of gastrin and secretin

“…Recently, it has been shown that the gastrointestinal hormone, gastrin, has a physiological role in the control of sphincter strength (5,6). Since a well-known relationship exists between gastrin and secretin in the hormonal control of gastric acid secretion (7)(8)(9)(10)(11)(12) and gastric motor function (13)(14), it seemed possible that these hormones also interact to regulate lower esophageal sphincter competence.…”

Is gastrin a major determinant of basal lower esophageal sphincter pressure? A double-blind controlled study using high titer gastrin antiserum.

“…The role of gastrin in the physiologic regulation of lower esophageal sphincter pressure (LESP)' is controversial (1)(2)(3)(4)(5)(6)(7)(8). Some observers have proposed that circulating gastrin (3,4) is the major determinant of LESP.…”