Plasma Gastrin Concentrations Research Articles

Inhibition of gastric acid secretion by a glycoprotein isolated from human urine (human urinary gastric inhibitor)

The gastric antisecretory activity of an inhibitor newly isolated from human urine (Human Urinary Gastric Inhibitor or HUGI) has been studied. HUGI was given intravenously and its activity determined in the following test systems: gastric secretion in the rat with pyloric ligation; gastric secretion in the dog with a Heidenhain pouch stimulated with pentagastrin, histamine and a protein meal; acid secretion by the isolated gastric mucosa of the rat; gastrointestinal motility; bile flow and gall-bladder tone and arterial and venous blood pressure and heart rate. HUGI was found to have marked activity only in the pyloric-ligated rats and in the dogs with Heidenhain pouches stimulated by a protein meal. Particularly in the dog, HUGI (0.1 to 6.4 μg/kg, i.v.) markedly inhibited gastric secretion, dose-dependently and without changing the plasma gastrin concentration. Negative results were obtained in the other tests, but these results serve to demonstrate that HUGI is an inhibitor well-differentiated from other glycoproteins or peptides with gastric antisecretory activity, such as urogastrone and GIP. The results obtained to date are not sufficient to allow the mechanism of action of HUGI to be defined.

Release of human pancreatic polypeptide and gastrin in response to intraduodenal stimuli: A case report

A recent clinical case afforded an opportunity to study the effects of duodenal stimulation on plasma human pancreatic polypeptide and gastrin concentrations, independent of gastric stimulation. A distension stimulus was provided by rapid injection of 100 ml of water and saline via a T-tube into an isolated duodenal afferent limb. In a third experiment, the saline contained 200 pg/ml of heptadeca-peptide human gastrin. Within 2 min after each injection, a rapid rise in circulating human pancreatic polypeptide levels appeared that fell promptly towards basal thereafter. Injections of 100 ml of Flexical, a supplemental tube feeding, resulted in a biphasic human pancreatic polypeptide response, the initial peak comparable to that seen following distension with water, saline, or saline containing gastrin, and a second peak of much greater magnitude and duration followed the initial peak. Plasma gastrin concentrations were not influenced following any of the stimuli. Duodenal distension alone may induce an early transient increase in plasma human pancreatic polypeptide concentrations, while intraduodenal nutrients per se may induce a later increment of greater magnitude and duration.

Effect of oral administration of calcium carbonate, Camalox and Novalucol on plasma gastrin concentration in duodenal ulcer patients.

In 6 patients having duodenal ulcer disease plasma gastrin concentrations were determined before and after the oral administration of 0.5--2 g of calcium carbonate, 2--4 tablets of Camalox and 2 tablets of Novalucol. No significant influence on basal plasma gastrin levels was noted indicating that antacids, whether they contain calcium carbonate or not, do not influence the basal plasma concentration of gastrin at occasional administration.

The role of the autonomic nervous system in the control of pancreatic endocrine responses to milk ingestion in the calf.

1. Pancreatic endocrine responses to ingestion of milk have been investigated in conscious unweaned calves, 3-5 weeks after birth. Passage of gastric content from abomasum to small intestine was prevented by means of a cannula placed in the duodenum adjacent to the pylorus and food was witheld for at least 22 h in order to deplete liver glycogen. 2. Under these conditions ingestion of milk was followed by a prompt rise in the concentrations of pancreatic glucagon, PP and gastrin in the arterial plasma but the usual rises in plasma glucose and insulin concentration were absent. 3. Evidence was obtained to show that absorption of glucose from the small intestine occurs sufficiently rapidly to account for the initial rise in plasma glucose concentration after feeding in normal animals. However, the rise in plasma glucagon concentration was sufficient to contribute to alimentary hyperglycaemia by promoting hepatic glycogenolysis in calves with abundant liver glycogen. 4. None of the neuroendocrine responses to ingestion of milk was affected by prior section of the splanchnic nerves whereas each was blocked by atropine (0.2 mg/kg), showing that all depend upon muscarinic, parasympathetic rather than sympathetic activity, in the absence of extraneous stress.

Effect of catecholamines on gastrin release

In vivo and in vitro techniques have been used to study the effect of catecholamines on gastrin release. The i.v. infusion of epinephrine in dogs produced a significant rise in plasma gastrin concentration. This response was prevented by the administration of propranolol to block β-adrenergic receptors. The infusion of isoproterenol, a β-adrenergic agonist, produced a significant rise in gastrin levels, while phenylephrine, an α-adrenergic agonist, had no effect. In in vitro studies using isolated pieces of rat antrum, isoproterenol stimulated acute phase release of gastrin, whereas phenylephrine was again without effect. The studies indicate that catecholamines directly influence G cell function.

Somatostatin inhibits gastric motility in response to distention.

Gastric motility and plasma gastrin concentration have been measured in 6 healthy volunteers before and after stepwise gastric distention. Distention was performed by filling a flaccid thin-walled bag, which was connected with a low pressure transducer for measuring intragastric pressure variations. Stepwise increase in gastric volume from 0-600 ml caused graded increases in gastric motility. No significant change was seen in the plasma gastrin level. When gastric distention was performed concomitantly with constant infusion of somatostatin (0.05 mg/h and 0.50 mg/h) in the same individuals on different days, motility was significantly reduced, without any changes in the plasma gastrin concentration. It is concluded that somatostatin, which probably plays a role in the gastro-intestinal tract, may have a physiological effect in the regulation of gastric motility too. This motility effect of somatostatin seems to be independent of any effect on the gastrin concentration.

The effect of gastrin on basal and aminoacid‐stimulated insulin and glucagon secretion in man

Abstract. The effect of gastrin on basal and aminoacid‐stimulated glucagon and insulin secretion was studied in eleven normal young subjects. The concentrations of glucagon, insulin and gastrin in plasma or serum were measured radioimmunochemically. The results of amino‐acid‐stimulation were compared to those obtained during a protein‐rich meal.Intravenous injection of synthetic human gastrin‐17 in doses from 15.6 ng to 1 μg/kg increased the concentration of glucagon and insulin in peripheral venous blood to a maximum within 5 min. In spite of the enhanced concentrations of insulin induced by gastrin, corresponding concentrations of glucose were either unchanged or increased. Infusion of a mixture of fifteen aminoacids increased the concentrations of glucose, glucagon and insulin. While the increases in glucose and insulin concentrations were similar to those obtained after a protein‐rich meal, the glucagon response was much larger after the infusion. Injection of gastrin‐17 after 30 min of infusion of aminoacids did not potentiate either the glucagon or the insulin response.The results indicate that gastrin, besides stimulating insulin secretion, can also stimulate glucagon secretion in a dose‐dependent manner. The concentrations of gastrin necessary to stimulate glucagon secretion significantly correspond to the concentrations found in diseases with endogenous hypergastrinaemia (achlorhydria and Zollinger‐Ellison syndrome). While gastrin potentiates the glucose‐induced insulin secretion, it does not potentiate neither the aminoacid‐induced insulin nor glucagon secretion.

Gastric Acid Secretion after Chronic Administration of the Anti-Secretory Agent Salbutamol in the Dog

Salbutamol is known to be a potent inhibitor of pentagastrin stimulated gastric acid secretion in both man and dog. This study describes the results, in both acute and chronic experiments in the dog, of salbutamol administration on gastric acid output and plasma gastrin concentration in response to a standard food stimulus. In the acute experiments, salbutamol in fusion reduced both gastric acid output and peak plasma gastrin concentration. In contrast, during chronic oral administration, salbutanmol caused a significant increase in the acid secretory response to the food stimulus; 2 weeks after the drug was stopped acid output has returned to control values. Only small changes in plasma gastrin concentration were found in the chronic study and these changes could not explain the increase in acid output.

The Effect of Somatostatin on Pentagastrin-stimulated Gastric Secretion and on Plasma Gastrin in Man

Three experiments were carried out in each of 6 healthy students on separate days, in a randomized order. Intravenous saline infusions were given for one hour basally in each experiment. During the second hour either pentagastrin, pentagastrin and somatostatin, or somatostatin alone were given. Gastric juice was collected continuously during all experiments. Somatostatin decreased the volume of gastric secretion and the concentrations of acid and pepsin, and output of acid, pepsin, and intrinsic factor (IF). The plasma gastrin concentration was not changed by somatostatin. A rebound effect was seen on pepsin and IF outputs after cessation of somatostatin, and on blood sugar concentration. The present study suggests that somatostatin acts on gastric secretion either directly or by mechanisms other than by inhibition of gastrin. The rebound of pepsin and IF indicates a release-inhibiting action on these substances similar to the effect of somatostatin on the release of some hormones.

Is there an Oxyntopyloric Reflex for Release of Gastrin in Man?

Plasma gastrin concentrations and gastric acid output were measured during graded balloon distention of the gastric fundus and body in 20 patients with duodenal ulcer. Acid output rose stepwise with increasing distention volumes but plasma gastrin remained unchanged. During intragastric neutralization in 5 of these subjects, fundic distention did not elicit a significant rise in plasma gastrin, whereas the acid response was similar to that observed in the control study when the gastric contents were acid. In 8 of the 20 patients, proximal gastric vagotomy profoundly suppressed the acid response to fundic distention. Basal plasma gastrin concentrations were elevated after vagotomy but were unchanged during graded fundic distention. The results suggest that neural reflex activation of the oxyntic glands is the main mechanism by which fundic distention stimulates acid secretion in man. The failure of fundic distention to release gastrin does not, however, completely rule out the existence of an oxyntopyloric distention reflex for gastrin release in man. Fundic distention in man seems to both stimulate acid secretion and induce an inhibitory mechanism acting on acid secretion. This inhibitory mechanism may, purely speculatively, also mask the effect of an oxyntopyloric reflex for gastrin release. The present study and earlier work suggest that in man distention of the stomach is a poor stimulus for release of gastrin, regardless of whether the pyloric or the oxyntic gland area, or both, are distended.

Simultaneous Measurement of Basal Pancreatic, Gastric Acid Secretion, Plasma Gastrin, and Secretin During Smoking

The effect of smoking one unfiltered cigarette every 15 min for 1 hr on basal gastric acid and pancreatic secretion was studied in 10 subjects with a history of duodenal ulcer and 10 without duodenal ulcer. Smoking induced a transient rise of basal acid output followed by a slight decrease. This effect was more pronounced in the duodenal ulcer group. Smoking markedly inhibited fluid and bicarbonate secretion during the smoking period. The bicarbonate and fluid secretion returned to control levels within 30 to 60 min in the ulcer group and in 60 to 90 min in the nonulcer group. There was no difference in the degree of inhibition of pancreatic secretion between the two groups. Immunoreactive gastrin and secretin in the peripheral venous blood did not change significantly during smoking. The degree of inhibition of basal pancreatic secretion correlated well with the plasma concentrations of nicotine. These observations indicate that smoking in the fasting state induces alterations of basal gastric and pancreatic secretions which are not related to changes in plasma gastrin and secretin concentration, but to plasma concentrations of nicotine. The implication of this study in relation to a possible causal association between cigarette smoking and peptic ulcer disease is discussed.

Lower Esophageal Sphincter Pressure in Cirrhotic Men with Ascites: Before and After Diuresis

Lower esophageal sphincter pressure (LESP) was measured in 10 biopsy-proved cirrhotics with esophageal varices and tense ascites before and after diuresis to evaluate of ascites might play in the development of variceal bleeding. In the 10 cirrhotic men studied, basal LESP was 30.9 +/- 1.7 mm Hg before and 22.7 +/- 1.3 mm Hg (P less than 0.01) after a diuresis which resulted in a mean 12-kg weight loss. LESP responses to abdominal compression were also evaluated. The change in LESP in response to a standard degree of abdominal compression was greater in the presence of ascites (8.5 +/- 0.4) than in its absence (6.3 +/- 0.4) (P less than 0.01). Basal gastric pH and fasting plasma gastrin concentrations did not differ during the two testing periods. Based on these data and the rarity with which cirrhotic patients with ascites complain of heartburn, it is concluded that reflux esophagitis caused by failure of the lower esophageal sphincter to remain competent is unlikely to be a significant etiological factor in the development of variceal bleeding.

Stimulatory effect of neurotensin on insulin and gastrin secretion in dogs.

The effects of synthetic neurotensin on plasma insulin and gastrin secretion were investigated in twelve normal and eight hypophysectomized (10th to 14th day post hypophysectomy) dogs. Neurotensin was injected rapidly or infused for 30 min into the superior pancreaticoduodenal artery, and plasma insulin and gastrin were measured by radioimmunoassay.In normal dogs, rapid administration of neurotensin (10μg/kg body wt) brought about a mild hyperglycemia and a rapid and sharp increase of plasma insulin and gastrin levels. In the pancreatic vein, a biphasic insulin response was noted. The same secretory pattern of insulin was demonstrated during neurotensin (500ng/kg/min) infusion. In the antral vein, the plasma gastrin level increased rapidly to 425% from basal level within 2 min and returned nearly to the initial level within 10 min after a rapid administration of neurotensin.In hypophysectomized dogs, the basal levels of plasma glucose, pancreatic insulin and antral gastrin were decreased to 53%, 9%, and 65% of normal dogs, respectively. Neurotensin has a little effect on insulin secretion, and a biphasic insulin secretory pattern observed in normal dogs was not demonstrated in hypophysectomized dogs. It seems likely that hypophysis may in part play a role in the neurotensin-induced insulin secretion. However, neurotensin-stimulated plasma gastrin concentrations were considerably maintained. Also, xenopsin (10μg/kg body wt) induced a mild hyperglycemia, hyperinsulinemia and hypergastrinemia, but its secretory activities were smaller than those of neurotensin.Neurotensin appears to stimulate the insulin and gastrin secretion by the mode action of neurogenic vasodilatation or by the direct action of pancreatic beta cell and gastrin secretory cell of the gastric antrum. Neurotensin may play an important role in the entero-insular axis.

Gastrin and Ulcer Disease: What Is Known

Although reports differ, no clear relationship has been shown between the high acid secretion in duodenal ulcers and basal plasma gastrin concentrations. Much recent attention has focused, therefore, on the concept of greater autonomy in gastrin secretion in patients with duodenal ulcer. The principal usefulness of gastrin determinations seems to be the ruling-out of the Zollinger-Ellison syndrome, and in case of recurrent ulcer, in which its use is limited.

The Effect of Antral Distension on Acid Secretion and Plasma Gastrin in Duodenal Ulcer Patients

The effect of antral balloon distension on acid secretion and the plasma gastrin concentration was studied in 8 duodenal ulcer patients. Antral distension significantly increased the acid secretion to about 30% of the peak acid response to pentagastrin without any change in the plasma gastrin concentration. Antral distension and concomitant intragastric neutralization, with the intention of facilitating release of antral gastrin, produced about the same acid response and did not evoke any plasma gastrin increment. The results suggest that the acid response to antral distension in duodenal ulcer patients is evoked without contribution of the gastrin mechanism, and that the acid response is probably mediated via a pyloro-oxyntic reflex. In this respect the duodenal ulcer patient seems to differ from the healthy subject, in whom antral distension produces no acid response, and from the dog, in which release of gastrin as well as pyloro-oxyntic reflex participate in the acid response to antral distension.

Gastric Secretory Response to Different Doses of Carbachol and Pentagastrin in Man

In 6 healthy students, the gastric secretion of acid, pepsin, and IF was measured during one hour at basal conditions, and during one hour of stimulation with 0.01 mug/kg/h and thereafter during one hour of stimulation with 0.1 mug/kg/h of pentagastrin. On separate days the same dose of pentagastrin was given in combination with 0.15 mug/kg/h or 1.5 mug/kg/h of carbachol, or stimulation was performed with each of the two doses of carbachol alone. A dose-dependent relationship was found between carbachol and the output of acid, pepsin, and IF. The responses to carbachol were independent of changes in plasma gastrin concentration. The acid- and IF-secretions stimulated by the largest dose of pentagastrin were significantly increased by the largest dose of carbachol, whereas the secretion of pepsin was not. Pentagastrin and carbachol seem to interact by competitive augmentation on the gastric secretion of acid and IF.

Effect of secretin on release of heterogeneous forms of gastrin.

The effect of an intravenous injection of secretin on plasma gastrin concentration is shown to be dependent upon the relative concentration of the major forms of immunoreactive gastrin present in the plasma at the time of injection. Secretin suppressed gastrin secretion in the fasting state in patients in whose plasma heptadecapeptide and big gastrins predominated and did not suppress when big big gastrin comprised more than 90% of plasma gastrin immunoreactivity. The post-secretin decrease in plasma gastrin was due entirely to the disappearance of the smaller, more rapidly degraded forms. Food-stimulated gastrin response was suppressed by secretin for the initial 40 minutes after a test meal but was greater than usual from 40 to 120 minutes.

Cardiovascular and endocrine responses to feeding in the young calf.

A number of cardiovascular and endocrine responses which occur during and after feeding in the unweaned calf are described. 2. There was a substantial increase in both heart rate and mean aortic blood pressure during feeding in these animals. This occurred within the first few seconds and persisted throughout the period of ingestion. 3. The concentrations of glucose, insulin and gastrin in arterial plasma rose abruptly during, or immediately after, feeding and elevated values persisted for at least 2 hr. A transient increase in glucagon concentration was also observed. In contrast, feeding appeared to produce no immediate rise in enteroglucagon concentration. 4. The adrenal output of glucocorticoids rose transiently in response to feeding but that of catecholamines was unaffected. 5. Cardiovascular responses to feeding were also examined in other species. In unweaned kids the changes were essentially similar to those observed in the calf but were less pronounced. In lambs a persistent hypertension occurred which was associated with a brief initial tachycardia. In adult dogs ingestion of solid food also caused tachycardia but although the aortic blood pressure rose for a short period at the beginning of feeding, hypotension developed thereafter. 6. The possibility that both the cardiovascular and endocrine responses, which occur during or immediately after feeding, are mediated by the autonomic nervous system is discussed.

Effect of bulbar acidification on basal secretion of acid and gastrin in dog.

Dogs were provided with mucosal septal pouches of the stomach and of the duodenal bulb. In some dogs a drainage gastric cannula was inserted into the most dependent portion of the stomach. In dogs which were found to secrete acid spontaneously during a control period at the start of each experiment, the bulbar puches were perfused with 0.1 M HC1 for 5-120 min. Bulbar acidification rapidly and profoundly reduced the basal acid output. In dogs which did not secrete acid spontaneously during the control periodbulbar pouches were perfused with 0.1 M HC1 for 1 h. Bulbar acidification did not significantly influence the plasma gastrin concentration and no acid was secreted from the Pavlov pouches following such acidification. The present results support the hypothesis that reduction of the intrabulbar pH may contribute to the reduction of acid secretion during interdigestive periods. The physiological significance of of mechanisms in the upper intestine which induce acid secretion following a reduction of the intraluminal pH is questioned.

Effect of urogastrone on gastric secretion and plasma gastrin levels in normal subjects.

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 mug urogastrone kg--1 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.