SUMMARY Purified human urogastrone was given by intravenous infusion to 12 normal volunteer subjects and measurements made of gastric acid, pepsin and intrinsic factor secretion, and of plasma gastrin concentration. Clinical, haematological, and biochemical screening tests were made throughout the period of study. Urogastrone inhibited acid and intrinsic factor secretion whether stimulated by pentagastrin, histamine, or insulin, but had a much less marked effect on gastric pepsin output. Plasma gastrin levels did not alter significantly. Limited dose-response studies showed that 0.25 ,g urogastrone kg-' hr-1 resulted in inhibition of acid output of 80 % and was not associated with clinical side-effects. No significant alteration in any of the haematological or biochemical measurements was observed in any of the subjects.
SUMMARY Our earlier observation that pentagastrin is a calcitonin (CT) secretagogue was confirmed and extended to include both synthetic human gastrin I and pure porcine gastrin II. The latter hormone was shown to stimulate the secretion rate of CT from thyroid preparations perfused in situ in anaesthetized pigs at concentrations (0·5 nmol/l) similar to those found after stimulation of gastrin production by a meat extract placed in the stomach (0·2 nmol/1). These concentrations of plasma gastrin are considerably less than those found in man in both pernicious anaemia and the Zollinger—Ellison syndrome, whereas the mean fasting plasma gastrin concentrations in normal human beings and pigs are similar. It is suggested that the comparatively high incidence of parathyroid hyperactivity in association with the Zollinger—Ellison syndrome may be a consequence of an increased CT secretion rate induced by hypergastrinaemia. Furthermore, the existence of a gastrointestinal—thyroid C cell system is proposed as an integral part of postprandial calcium homeostasis.
The role of calcitonin (CT) in postprandial calcium homeostasis and the possibility of a gastroentero-thyroid C-cell system was studied in young pigs. When pigs were fasted for more than 36 h and then fed, the plasma calcium concentration decreased by 6\m=.\1 % over a period of 60\p=n-\120 min after a meal. Since in thyroidectomized pigs the plasma calcium concentration increased by 7\m=.\2 % when they were fed after a fast of 36 h it is suggested that increased CT secretion assists in the control of postprandial hypercalcaemia. Direct measurement of CT in peripheral plasma supported this suggestion. Because the plasma calcium concentration in an intact pig on a normal feeding regime does not change after a meal, the possibility of the involvement of one or more humoral factors in the stimulation of thyroid C-cells was investigated. Exogenous gastrin and endogenous gastrin stimulated by meat extract were both previously shown by us to increase CT secretion rate. This observation has now been extended to include other stimuli to endogenous gastrin, e.g. glycine and gastric distension. Furthermore, partially purified enteroglucagon increased CT secretion rate from perfused thyroid glands, isolated in situ. Stimulation of endogenous entero\x=req-\ glucagon by the intraduodenal administration of glucose, and probable stimulation of endogenous pancreozymin by intraduodenal fat, were both associated with an increased CT secretion rate from the thyroid gland.These results support the concept of a gastroentero-thyroid C-cell system which serves to stimulate CT secretion and thus to protect the skeleton from excessive bone resorption during periods of dietary sufficiency.
SUMMARY A one-hour infusion of 0.25 ,ug/kg urogastrone administered to seven patients with duodenal ulceration resulted in significant reduction of basal acid secretion (p<005) but was without significant effect on basal pepsin and intrinsic factor secretion or on serum gastrin concentration. In another group of five patients with duodenal ulceration a one-hour infusion of urogastrone was given on five successive days. On day 1 and 5 urogastrone was administered after establishing a plateau response to intravenous pentagastrin 1.2 ,ug/kg/h. A mean reduction of 65% in acid output during the urogastrone infusion was seen on day 1 and this was maintained during the next hour. On day 5 the pentagastrin-stimulated acid output was less than on day 1 and a further significant decrease was noted after urogastrone. Pepsin and intrinsic factor output were also significantly inhibited. There was no change in fasting serum gastrin or urogastrone concentration.Urogastrone has recently been extracted from human material and, although two pure polypeptides were obtained, these were shown to be the same, apart from one additional amino acid.' Studies in humans have been carried out using mixture of the 52 and 53 amino acid residue peptides which have the same biological actions. Studies in normal volunteers2 showed that urogastrone (0.25 1Lg/kg/h intravenously) inhibited secretagoguestimulated acid secretion with no effect on serum gastrin concentration. In patients with ZollingerEllison syndrome3 there was marked inhibition of acid secretion and a rise in serum gastrin concentration. In addition, patients with ZollingerEllison syndrome experienced pain relief during the urogastrone infusion and for up to 24 hours afterwards.As urogastrone has been found to be virtually free from unwanted side-effects in these human studies and in extensive animal trials over many years, it is possible that it may have a role in the treatment of peptic ulceration. It was therefore considered important to evaluate its effect on gastric secretion ' Address for correspondence: C. G. Koffman, Leighton Hospital, Middlewich Road, Crewe CWI 40J. Received for publication 26 February 1982 and serum gastrin concentration in patients with active duodenal ulceration both in the basal and pentagastrin-stimulated state. We have also investigated the possibility of a cumulative effect of repeated urogastrone infusions. Methods PATIENTSTwelve male patients with chronic duodenal ulcer took part in this study and informed consent was obtained in each case. The diagnosis was confirmed in each patient both by barium meal and duodenoscopy which was always performed within seven days of the start of the study. Only patients with no history of physical signs of disease of any other major system were included, and no patient had previously undergone gastric surgery. In addition, no patients received H2-receptor antagonists within two weeks of the study. Another five patients with duodenal ulceration underwent pentagastrin infusion over a three-hour period in order ...
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