Effect of Hepatic Transit of Gastrin, Pentagastrin, and Histamine Measured by Gastric Secretion and by Assay of Hepatic Vein Blood

Thompson, James C.; Reeder, David D.; Davidson, Warren D.; Charters, A C; Brückner, W. L.; Lemmi, Carlos A.E.; Miller, James H.

doi:10.1097/00000658-196909010-00017

Cited by 41 publications

(6 citation statements)

References 16 publications

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“…They are in keeping with the results of Gillespie and Grossman (1962), Clarke, Hall, Devor, and Rizer (1967), Lick, Welsch, Hart, Bruckner, Balser, and Gurtner (1967) and McGuigan, Jaffe, and Newton (1970). Thompson, Reeder, Davidson, Charters, Bruckner, Lemmi, and Miller (1969) found that acid secretion from gastric fistulae in conscious dogs was similar during jugular vein and portal vein infusions of gastrin, but they found a 46 % loss of gastrin across the liver when portal and hepatic vein levels were measured by radioimmunoassay. This suggests that there may be biologically active gastrin derivatives in the hepatic vein blood which are not immunoreactive.…”

Section: Discussionsupporting

confidence: 87%

Disappearance of gastrin and pentagastrin in the portal circulation

Temperley¹,

Stagg²,

Wyllie³

1971

Gut

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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

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Section: Discussionsupporting

confidence: 87%

Disappearance of gastrin and pentagastrin in the portal circulation

Temperley¹,

Stagg²,

Wyllie³

1971

Gut

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“…Evidence has been presented that in dogs synthetic human gastrin may be inactivated in vivo by the kidney (Clendinnen, Davidson, Reeder, Jackson, and Thompson, 1969) and the liver (Thompson, Reeder, Davidson, Charters, Bruckner, Lemmi, and Miller, 1969), and in vitro by the lung, skeletal muscle, and gastric fundus mucosa (Thompson, Reeder, Davidson, Jackson, and Clendinnen, in press). Of these sites the kidney is believed to be the most efficient (Clendinnen et al, 1969).…”

mentioning

confidence: 99%

Effect of nephrectomy on the rate and pattern of the disappearance of exogenous gastrin in dogs

Bg¹,

Dd²,

En³

et al. 1973

Gut

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SUMMARY Studies of gastrin metabolism were performed in four dogs before and after nephrectomy. Synthetic human gastrin I was infused for two hours and serum samples were obtained at various times during and after infusion. Serum concentrations of gastrin were measured by radioimmunoassay. A two-compartment model was employed to calculate half-lives under each of four experimental conditions, low and high infusion rates, used both before and after nephrectomy. The model half-life was greatly prolonged after nephrectomy at both infusion rates (from 2.54 min to 5.15 min at the low rate, and from 2.85 min to 7.88 min at the high rate). The metabolic clearance rate, an expression of the rate of catabolism during infusion, decreased significantly after nephrectomy at both infusion rates. These observations indicate that the kidney is an important organ for the catabolism of exogenous gastrin.Synthetic human gastrin I has been shown to have a short half-life when it is infused into dogs (Reeder, Jackson, Brandt, and Thompson, 1972b). This is in accordance with the brief physiological action that infusions of gastrin II have in man (Makhlouf, McManus, and Card, 1966).Evidence has been presented that in dogs synthetic human gastrin may be inactivated in vivo by the kidney (Clendinnen, Davidson, Reeder, Jackson, and Thompson, 1969) and the liver (Thompson, Reeder, Davidson, Charters, Bruckner, Lemmi, and Miller, 1969), and in vitro by the lung, skeletal muscle, and gastric fundus mucosa (Thompson, Reeder, Davidson, Jackson, and Clendinnen, in press). Of these sites the kidney is believed to be the most efficient (Clendinnen et al, 1969).The effect of nephrectomy on the half-life of circulating exogenous gastrin in dogs has been determined by measuring the rate of disappearance MethodSynthetic human gastrin I was infused in four healthy, alert mongrel dogs weighing 17-22 kg. A catheter for infusion was placed in the superior vena cava and a catheter for sampling was inserted in the iliac vein. Synthetic human gastrin I was given to the fasting dogs according to two dosage regimens. The low dose consisted of a loading injection of 4 micrograms (pg), followed immediately by infusion at the rate of400 nanograms (ng)/kg/hour for two hours. The high dose was 8 ,ug given as a load and 800 ng/kg/hour infused for two hours. These two infusions, given in random order, were separated by a rest period of two days. Infusion of gastrin at these rates resulted in nearly constant values for serum gastrin after one hour. Two basal serum samples for gastrin measurement were obtained before the administration of exogenous gastrin. Additional samples were obtained at the end of the infusion (time zero), and at one, two, three, four, five, eight, 10, 15, 30, and 60 minutes thereafter. One week after the completion of these experiments, both kidneys were removed under general anaesthesia. The dogs were then allowed to recover for two days 462 on 12 May 2018 by guest. Protected by copyright.

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“…Gastrin is among the factors held to be responsible (Gregory 1958, Clarke et al 1958a. However, gastrin is not degraded in the liver (Thompson et al 1969, Reeder et al 1972, Dencker et a/. 1973, and in the rat the postprandial serum gastrin concentration is actually reduced after portacaval shunting (Reichle et al 1974, Alumets et al 1980).…”

Section: Introductionmentioning

confidence: 99%

Effects of portacaval shunt on the rat stomach

Ekelund

Håkanson

Holmin

et al. 1985

Acta Physiologica Scandinavica

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In portacaval-shunted rats, basal but not pentagastrin-stimulated acid secretion was higher than in sham-operated controls. The basal serum gastrin concentration was unchanged and the postprandial serum gastrin concentration lowered following portacaval shunt. Thus, gastrin is not responsible for the elevated basal acid secretion. The present study provides evidence that there is no trophic effect on the oxyntic mucosa as a whole and that there is no change in parietal cell-associated gastrin receptors after portacaval shunting. Interestingly, however, endocrine cells in the oxyntic mucosa (the histamine-containing ECL cells) proliferated greatly and the pentagastrin- and cholecystokinin octapeptide-induced activation of the histamine-forming enzyme, histidine decarboxylase, in these cells was much greater than in control rats. Analysis of the dose-response curves for the enzyme-activating effect of pentagastrin and cholecystokinin-octapeptide indicated that the D50 values for these two stimulants were not altered by shunting but that the maximal enzyme activation was greatly elevated. The enhanced enzyme activation can be partly, but not fully, explained by the fact that the ECL cells were increased in number. The enhanced response following portacaval shunt probably reflects also an increased number of gastrin receptors per ECL cell. The effect of portacaval shunting on gastric ECL cells can perhaps be explained by impaired degradation in the liver of intestinal substance(s) exerting a highly specific trophic effect on the ECL cells or, alternatively, causing an enrichment of gastrin receptors on these cells, thereby making them more sensitive to the trophic effect of gastrin. The ECL cell hyperplasia is manifest about 4 weeks after the shunting. A modified procedure for portacaval shunting which left the gastroduodenal vein (otherwise ligated) drained to the liver produced the same trophic effect as conventional portacaval shunt, suggesting an intestinal rather than gastroduodenal origin of the agent(s) responsible for the trophic action.

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Effect of Hepatic Transit of Gastrin, Pentagastrin, and Histamine Measured by Gastric Secretion and by Assay of Hepatic Vein Blood

Cited by 41 publications

References 16 publications

Disappearance of gastrin and pentagastrin in the portal circulation

Disappearance of gastrin and pentagastrin in the portal circulation

Effect of nephrectomy on the rate and pattern of the disappearance of exogenous gastrin in dogs

Effects of portacaval shunt on the rat stomach

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