Disappearance of gastrin and pentagastrin in the portal circulation

Abstract

SUMMARY Experiments on dogs and rats showed that synthetic human gastrin I was inactivated in the small bowel but not in the liver, whereas pentagastrin was rapidly inactivated by the liver. Similar results were obtained with tissue homogenates. The significance of these results is discussed in relation to the probably increased incidence of peptic ulceration following extensive small-bowel resection in man.The physiological and pharmacological actions of the hormone gastrin and of its synthetic analogue pentagastrin1 have been extensively studied. Gastrin may be involved in the causation ofpeptic ulceration, and pentagastrin is now widely used as a gastric stimulant in tests of acid secretion, but little is known of the fate of either compound in the body. Since the blood concentration of a hormone or a drug depends on its rate of removal from the circulation as well as the rate at which it enters the circulation, it is important to study the fate of active substances in the body. For example, excessive levels of gastrin might be present in the blood even though the antrum secreted normal amounts; this could occur if the mechanism for removing gastrin were impaired. We have therefore devised experiments to investigate the inactivation of gastrin and pentagastrin by the liver and small bowel. In choosing to study the fate of these compounds in the portal circulation we were guided by the concept originally proposed by Elliott (1905) that hormones disappear in the tissues they excite. The experiments were performed on anaesthetized dogs and rats, and in vitro with homogenates of rat liver and small bowel mucosa. Methods EXPERIMENTS IN DOGSTen adult mongrel dogs weighing 6-16 kg were anaesthetized with intravenous pentobarbitone (25 mg/kg body weight), and mechanically respired. In all the dogs wide bore cannulae were placed in the 1Peptavlon, ICI Ltd.Received for publication 16 March 1971. pyloric antrum and the fundus of the stomach. Ligatures were tied around the pylorus and the oesophagus, care being taken in the latter case to exclude the vagi. During experiments the dog lay on its left side and the cannulae were placed so that fluid introduced into the pyloric cannula drained by gravity through the stomach and was all recovered from the fundal cannula. Fine

Distribution and Metabolism of Gastrin

“…evidence also exists for alternative routes of gastrin metabolism [16,25,26]. The accumulation of activity in the small bowel which was found in the present study after injection of l2SI-gastrin in nephrectomized animals is consistent with earlier reports of gastrin degradation capacity in the small bowel [2,26].…”

Management of patients with a short bowel

“…In man some cases of long-term survival in patients with a short bowel has been attributed to their previous gastric surgery [43][44][45] . High circulating gastrin levels are observed [40,46,47] and may be due to less small bowel being available to catabolizegastrin [48,49] . Gastric acid hypersecretion could increase the incidence of peptic ulceration [50] ; impair nutrient absorption by causing bile salt precipitation [51] ; reduced pancreatic enzyme function and increased jejunal motility.…”

The Effects of Glucagon, Secretin, Pancreozymin and Pentagastrin on the Hepatic Arterial Vascular Bed of the Dog

“…In contrast to the three naturally-occurring hormones, the hepatic vasodilator activity of pentagastrin on i.a. infusion was not maintained, a reflection, perhaps, of its rapid deactivation by the liver (Thompson, Reeder, Davidson, Charters, Bruckner, Lemmi & Miller, 1969;Temperley, Stagg & Wyllie, 1971). Because of the rapid decline of the vasodilator response to pentagastrin any alteration of the hepatic arterial vasoconstrictor properties of noradrenaline was difficult to ascertain in these experiments.…”