Pentagastrin Infusion Research Articles

Effect of Enteric Hormone's on Sphincter of Oddi and Gastrointestinal Myoelectric Activity in Fasted Conscious Opossums

In this study we evaluated the effect of enteric hormones on sphincter of Oddi and gastrointestinal spike burst frequency in fasted conscious opossums. A chronic model for obtaining multiple long-term recording of sphincter of Oddi and gastrointestinal myoelectric activity was prepared in 12 animals by implanting bipolar electrodes in the gastric antrum, duodenum, sphincter of Oddi, jejunum, and ileum. Subsequently, 8-18 recording session, 6-8 h in length, were obtained in each animal. Each study was preceded by a 15-h fast. After recording two cycles of the interdigestive migratory myoelectric complex, a 60-min infusion of saline, cholecystokinin-octapeptide, pentagastrin, glucagon, or secretin was begun early in the quiescent period of duodenal activity, 10 min after termination of phase 3 of the migratory myoelectric complex activity. Cholecystokinin-octapeptide (10-80 ng/kg . min) and pentagastrin (25-200 ng/kg . min) increased sphincter of Oddi spike burst frequency while converting interdigestive gastrointestinal myoelectric activity to a fed-like pattern of continuous, irregular spike bursts. Glucagon at high doses of 500 and 1000 ng/kg . min depressed sphincter of Oddi and gastrointestinal spike burst activity, whereas lower doses of glucagon and secretin (3-12 CU/kg . h) had no effect. We conclude that in the opossum, relatively low doses of cholecystokinin-octapeptide and pentagastrin stimulate sphincter of Oddi and gastrointestinal spike burst activity while disrupting the cyclic pattern of sphincter of Oddi and gastrointestinal spike burst activity present during fasting. The physiological significance of these findings remains to be determined.

A study on the effects of clinical drugs on lower esophageal sphincter pressure. Particularly on the relation with clinical drugs

Lower esophageal sphincter pressure (LESP) in man was measured by using a miniature semiconductor pressure sensor and the effects of clinical drugs on lower esophageal sphincter (LES) were examined. In total, 183 clinical cases were studied; 88 cases as controls, 38 esophagitis cases, 31 gastric ulcer cases, 21 duodenal ulcer cases, 4 liver cirrhosis cases and 1 scleroderma case. Drugs studied were pentagastrin, metoclopramide, domperidone, NaHCO3, maalox, cimetidine, secretin, glucagon, nifedipine, and nicardipine hydrochloride. There results obtained were as follows.Continuous intravenous drip infusion of pentagastrin (12μg/min) tentatively raises LESP. Also both metoclopramide and domperidone showed a tentative LESP-raising effect when administered either intravenously (10mg) or orally (10, 20mg) . The peak of the effect was 3-10 minutes after the intravenous injection and 20-30 minutes after the oral administration. The effect of oral administration lasted long and its effectiveness was as good as that of an intravenous injection. NaHCO3 and maalox also raised LESP tentatively. The ordinary dose of NaHCO3 (1.0g) or maalox (10ml) had the effect of raising LESP for approximately 30 minutes. LESP raising effect of intravenously injected cimetidine (200mg) was not clear. An intravenous injection of secretin (1u/kg) or glucagon (1.0mg) clearly lowered LESP. Also, orally administered nifedipine (10mg) or nicardipine hydrochloride (10mg) tentatively lowered LESP. LESP-lowering effect of nifedipine was tentatively inhibited by metoclopramide.

Calcitonin—C.N.S. action to control the pattern of intestinal motility in rats

Synthetic calcitonin injected into the lateral ventricles (ICV) of rats at picomolar concentration restores the “fasted” motility pattern of the small intestine in fed rats at doses as low as 0.083 picomoles. This effect which appeared in less than 5 min and persisted at least 2 hours for 0.83 picomole, was blocked by a previous intraventricular administration of 10 μg of calcium gluconate. At 0.83 picomole ICV, calcitonin also suppressed the disruption of the “fasted” pattern induced by intravenous infusion of Pentagastrin (6 μg·kg −1·h −1) but not that induced by insulin (0.5 U·kg −1). These findings support the hypothesis that calcitonin acts centrally to control the pattern of intestinal motility by inhibiting the digestive influences responsible for the “fed” pattern. All of these peripheral influences are mediated by a Ca ++ sensitive central structure.

Haemonchus contortus: Egg laying influenced by abomasal pH in lambs

Abomasal and duodenal concentrations of Haemonchus contortus eggs were measured in four lambs fitted with permanent abomasal and duodenal cannulas and infected with 25,000 Haemonchus contortus larvae. During the period of maximal egg laying, i.e., when the abomasal H. contortus egg concentration was above 2000 eggs/ml, the animals received cimetidine (20 mg/kg) intravenously or pentagastrin (5 μg·kg −1·h −1) for 90 min and the changes in abomasal and duodenal egg concentrations were followed for 2.5 hr. Pentagastrin infusion reduced the abomasal and duodenal pH significantly and in less than 15 min decreased the abomasal and duodenal egg concentrations which represented only 21.4 and 12.0% of the control values at the end (90 min) of infusion. During pentagastrin infusion, both the abomasal ( r = 0.56, P ⩽ 0.01) and the duodenal ( r = 0.72, P ⩽ 0.01) egg concentrations correlated positively with the corresponding pH values. After cimetidine injection, the abomasal and duodenal pH had increased 150 min later to, respectively, pH 6.16 and 6.27. During the first 30 min for an abomasal pH lower than 4.5–5.0, egg production increased by 106%; then the abomasal and duodenal egg concentrations decreased progressively, representing, respectively, only 39.3 and 16.4% of the control values 120 min later. It is concluded that the level of egg laying of adult H. contortus was related to the abomasal acidity, the maximal egg production occurring when the abomasal pH was between pH 4 and 4.5.

Regulation of oxygen uptake in resting and pentagastrin-stimulated canine stomach.

The relation between oxygen uptake and blood flow in the isolated dog stomach was investigated under resting conditions and during intra-arterial infusion of isoproterenol or pentagastrin. Blood flows above and below control values were achieved by pump perfusion and partial arterial occlusion, respectively. In the resting stomach oxygen uptake increased from 0.4 to 1.5 ml.min-1.100 g-1 as blood flow increased from 4 to 40 ml.min-1.100 g-1 and then remained constant for blood flows up to 100 ml.min-1.100 g-1. Isoproterenol did not significantly alter the relation between oxygen uptake and blood flow. In pentagastrin-stimulated stomachs oxygen uptake was maintained at 2.5 ml.min-1.100 g-1 at blood flows between 40 and 100 ml.min-1.100 g-1 and decreased at blood flows below 40 ml.min-1.100 g-1. The results indicate that pentagastrin increases oxidative metabolism in the stomach. Despite this increase in oxygen consumption with pentagastrin, the general shape of the relation between blood flow and oxygen uptake remained the same and was simply displaced vertically above the control data.

Effect of pentagastrin on parietal cell ultrastructure in glucagon-pretreated subjects.

The effect on parietal cells of glucagon given prior to pentagastrin is unknown. Fifteen healthy volunteers were studied during constant intravenous infusion of pentagastrin (2 micrograms/kg body weight/hr) and during pentagastrin infusion initiated 20 min after intravenous injection of 2 mg glucagon. Three types of studies were performed: Gastric mucosal biopsies were obtained with a Quinton instrument. Electron micrographs of 320 parietal cells were analyzed by the Loud quantitative method, and intragastric pH (pH probe), or gastric potential difference (PD) were recorded continuously. Pentagastrin infusion produced a significant increase in canalicular and simultaneous reduction of tubulovesicular membrane area of parietal cells. Glucagon pretreatment did not inhibit canalicular and tubulovesicular membrane reaction to pentagastrin; unexpectedly this reaction was significantly greater when compared to that after pentagastrin alone. Initiation of pentagastrin infusion in subjects pretreated with glucagon produced a greater absolute value drop in gastric PD (23 +/- 2 mV) and an earlier drop in intragastric pH (3 min) than in subjects receiving pentagastrin infusion alone (13 +/- 1 mV and 10 min, respectively). In conclusion, at the doses studied, glucagon pretreatment increases parietal cell canalicular reaction to pentagastrin.

Decrease of plasma somatostatin-like immunoreactivity and increase of gastrin and insulin levels in peripheral venous blood of conscious dogs following infusions of pentagastrin. The possible role of vagal "gastrinergic" fibres as inhibitors of gastrointestinal somatostatin release.

Somatostatin has been shown to exert inhibitory actions on gastric acid secretion, gastrointestinal motility and on the release of gastrointestinal and pancreatic hormones. Furthermore, somatostatin is produced and stored in endocrine cells in the corporeal and antral parts of the stomach and in the pancreas, indicating that endogenous somatostatin might take part in the control of gastrointestinal and pancreatic functions. (For a review on the subjects see Efendic, Luft & Uvnäs‐Wallensten 1982.)

Control of the antral motor response to feeding by gastric acid secretion in rats.

1. The motor response of the antrum to feeding was examined in relation to gastric acid content in six adult rats fitted with electrodes and strain gauges on the antrum, two of them also having a small cannula in the fundus. 2. After fasting overnight, feeding was accompanied by an immediate increase in antral activity of seventeen to nineteen strong contractions lasting 5.33 +/- 1.15 min. Both the duration and amplitude of this antral motor response were increased 2 hr after ingestion of cimetidine (20 mg/kg) or 60 min after intramuscular administration of the same dose of proglumide. 3. By contrast, the response to feeding was reduced by 43% in duration and by 58% in amplitude during an intravenous infusion of pentagastrin (5 mg/kg per hr) and disappeared after an infusion of HCl into the stomach. The area under the curve of the pressure developed by the gauge, used as a motility index, was nearly doubled when the pH of the gastric contents increased from 3.1 to 5.7 and was halved when the pH decreased from 3.1 to 2.2. 4. In normal or inhibitory gastric acid secretion, the blockade of the antral motor response to feeding appeared when the total acid content of the gastric juice reached 35-70 mu equiv/ml. 5. The results indicated that the rate of gastric secretion is of paramount importance in regulating the magnitude of the antral motor response to feeding. It is suggested that the vagally stimulated antral motility is rapidly counteracted by the increased acid secretion.

Effect of dopamine on pentagastrin-stimulated gastric antral motility in dogs with gastric fistula.

The purpose of the present study was to evaluate the effect of dopamine on gastric antral motility in conscious dogs with gastric fistula by using miniature strain-gauge transducers. Infusion of pentagastrin changed the contractile activity to a digestive state. Dopamine, an endogenous catecholamine, was used alone and in conjunction with selective blockade or adrenergic and dopaminergic receptors. The stimulated antral motility was inhibited by dopamine. The effect was significantly blocked by the peripherally acting dopaminergic blocker domperidone and by cis-flupenthixol, which blocks both peripheral and central dopaminergic receptors. The effect of dopamine was not significantly altered by the beta 1-adrenoceptor blocker practolol, the alpha-adrenoceptor blocker phentolamine, or the alpha + beta-adrenoceptor blocker labetalol. Consequently, this study indicates that dopamine acts on gastric antral motility through dopaminergic receptors. beta-Adrenergic receptors, which are active in the impairment of gastric acid secretion, seem not to be involved in the motility response.

Effect of thyrotropin-releasing hormone on gastro-intestinal secretions in dogs

Thyrotropin-releasing hormone (TRH) immunoreactivity has been shown previously to be distributed throughout the gastrointestinal tract and the pancreas. This study demonstrated that TRH given intravenously suppresses, in a dose-related manner, sham-feeding induced food intake and inhibits gastric secretion provoked by infusion of pentagastrin or instillation of 10% liver extract into the stomach. TRH also reduces pancreatic response to secretin, caerulein, feeding a meat meal or duodenal acidification. The findings that TRH inhibits gastric and pancreatic secretions induced by exogenous and endogenous stimulants, and that the inhibition by TRH of post-prandial secretion is not accompanied by any change in serum gastrin, indicate that TRH probably acts directly on the exocrine stomach and pancreas.

Aspirin-induced gastric ulcers in cats. Prevention by prostacyclin.

Gastric ulcers were produced in conscious cats in 3 hr by simultaneous intravenous or intragastric administration of acetylsalicylic acid (ASA), plus intravenous infusion of histamine (80 micrograms/kg/hr), pentagastrin (8 micrograms/kg/hr), or intragastric instillation of HCl. The formation of these ulcers was accompanied by almost complete inhibition of prostaglandin (PG) biosynthesis, suggesting that the withdrawal of normal protection of gastric mucosa by PGs may be major factor in pathogenesis of ASA-induced gastric lesions. Prostacyclin (PGI2), infused at a dose producing about 50% inhibition of histamine or pentagastrin-induced acid secretion, significantly reduced the formation of gastric ulcers produced by ASA + histamine or pentagastrin. Inhibition of gastric acid secretion by about 50% using ranitidine, a new H2-receptor antagonist, also decreased the formation of gastric ulcers induced by ASA + gastric secretagogue, but the degree of this reduction was significantly smaller than after PGI2. In addition, PGI2 decreased significantly the severity of gastric ulcers produced by a combination of ASA plus gastric perfusion of HCl, the antiulcer effect being more pronounced when PGI2 infusion was started prior to, rather than during, ASA administration. This study confirms that the administration of ASA plus gastric secretagogue or gastric instillation of HCl is a reliable model of gastric ulcerations probably resulting from withdrawal of biosynthesis of mucosal PGs and shows that PGI2 is capable of preventing the formation of these ulcers by means other than its effect on gastric acid secretion.

Influence of Desalivation on Acid Secretory Output and Gastric Mucosal Integrity in the Rat

Exogenous administration of substances extracted from rodent salivary glands may increase the resistance of gastric mucosal barrier to the disruptive actions of ulcerogenic agents and/or reduce acid secretory output. In the present study the influence of desalivation in the rat on acid secretory function and mucosal integrity has been investigated. Experiments were performed on rats 4 wk after removal of the major salivary glands and ligation of the salivary ducts. Intravenous infusion of pentagastrin (0.1--0.4 microgram/kg/min) resulted in an increase in acid output in desalivated rats although the responses was less than that observed in sham-operated controls. Intraluminal instillation of a bile salt solution (5 mM in 150 mM HCl) in control animals resulted in a significant loss of H+ and the luminal appearance of Na+ and K+. The net fluxes of Na+ and K+ were exacerbated in the desalivated group. Furthermore, the mean area of bile salt-induced ulceration was significantly greater in desalivated rats than in the control group. In the absence of bile salt treatment there was no difference in either the transmural ionic fluxes or area of ulceration between the two groups. These results suggests that removal of the major salivary glands in rats decreases the resistance of the gastric mucosa to bile salt-induced damage.

Infusion of Vasoactive Intestinal Polypeptide in Man: Pharmacokinetics and Effect on Gastric Acid Secretion

Elimination and effect on acid secretion of vasoactive intestinal polypeptide (VIP) were studied in six healthy volunteers. On a background infusion of pentagastrin, 100 ng/kg-h, VIP was administered as stepwise intravenous infusions in doses of 0.5, 0.9, and 2.7 micro/g/kg-h, each dose being give for 1 h. Mean plasma VIP concentrations rose from 5.7 pmol/l to 28, 106 and 336 pmol/l during the VIP infusions. No significant changes in acid secretion occurred during VIP infusion as compared to infusion of pentagastrin alone, and no duodeno-gastric reflux was registered. Serum gastrin concentrations were unaltered during VIP infusion. Elimination of VIP was bi-exponential with half-lives of 2 and 21 min, respectively. Metabolic clearance rate was 42 ml/kg-min and the estimated volume of distribution 135 ml/kg.

Abnormal gastric emptying response to pentagastrin in duodenal ulcer disease

The effect of pentagastrin on gastric emptying in duodenal ulcer disease (DU) is unknown. The evaluation of this effect is complicated by the simultaneous action of the hormone on gastric secretion. We compared gastric emptying and net gastric output in 17 patients with active DU to that of 11 healthy controls. A dye-dilution technique was used to determine net acid output, fractional emptying rate, and acid emptying rate during a basal period and after pentagastrin (6 microgram/kg/hr, intravenously). Net basal acid output observed in controls (54 +/- 10 microEq/min; mean +/- SE) was used as the primary criterion for separating DU patients into 12 normosecretor (30 +/- 10 microEq/min) and 5 hypersecretor patient groups (163 +/- 40 microEq/min). The pentagastrin-stimulated net acid output was significantly greater in hypersecretor patients than in controls (P less than 0.01) but was normal in normosecretor patients. Basal fractional emptying and acid emptying rates were significantly greater in hypersecretors than in controls (P less than 0.05) but were normal in normosecretors. In contrast, both normo- and hypersecretor patients had significantly greater fractional emptying (P less than 0.01) and acid emptying rates than controls (P less than 0.05) during pentagastrin infusion. Thus, a greater load of acid transiently enters the duodenum in duodenal ulcer disease following pentagastrin stimulation, even in the absence of gastric hypersecretion.

Pentagastrin in diffuse oesophageal spasm.

The effect of pentagastrin on oesophageal motility was studied in six subjects with idiopathic diffuse oesophageal spasm (IDOS). Pentagastrin was administered by continuous intravenous infusion in doses of 1 microgram/kg/h, 5 micrograms/kg/h, and 10 micrograms/kg/h. Saline infusion was used as a control. No subject experienced pain during pentagastrin infusion. Two developed dysphagia and repetitive contractions with 'wet' swallows during the saline infusion and the lowest pentagastrin infusion. Contraction amplitude was increased only with 'dry' swallows during the 10 micrograms/kg/h infusion period. Contraction duration was increased with both 'wet' and 'dry' swallows during the 1 microgram/kg/h infusions, and with 'dry' swallows during the 10 micrograms/kg/h infusion. Propagation velocity was not altered by pentagastrin. We conclude that gastrin released physiologically by eating probably does not contribute to symptom production in IDOS. Moreover, it seems unlikely that pentagastrin, at least in these doses, can be exploited for diagnostic purposes.

Release of prostaglandin E 2 into gastric juice during stimulation of muscarinic- and gastrin receptors in dogs and in humans

To investigate the causal relationship, if any, between gastric PG formation and gastric acid output, the release of PGE 2 into gastric juice has been studied in eight beagle dogs with a gastric fistula, using sustained half-maximal stimulation by bethanechol and pentagastrin, and in eight duodenal ulcer patients, using the combined sham feeding/pentagastrin test. Immunoreactive PGE 2 was determined by a method validated by gas chromatography-mass spectrometry and PGE 2 values were normalized by expressing them as ng PGE 2 released per meq H + secreted. In the dogs “steady state” PGE 2 output (0.4–10 ng/meq H +) was interrupted during continous i.v. pentagastrin infusion by symmetrical peaks (50–60 minutes of duration) with a maximum of 24±3.1 ng/meq H + (mean±SEM). During bethanechol stimulation the rhythmic variations were smaller, but the median values for the periods 30 to 180 or 240 minutes significantly ( p < 0.01) higher (3.9–46 ng/meq H +) than in pentagastrin experiments (0.8–20 ng/meq H +). In humans the peak PGE 2 output during sham feeding (3.4–41 ng/meq H +) was significantly ( p < 0.02) larger than following bolus stimulation (6 ug/kg) by pentagastrin (2.2–18 ng/meq H +). The findings are consistent with the hypothesis that activation of muscarinic receptors represents the physiologic mechanism by which gastric release of PGs is regulated. Cyclic variations in gastric PG formation appear to occur in response to vagal stimulation since the peaks in PGE 2 output were preceeded by increased myoelectrical activity (i.e. mean contractile index).

A study of the effect of antral distension on gastric acid secretion in man.

In 30 healthy subjects distension of the antrum by a 150-cm3 balloon reduced the acid and volume responses to submaximal stimulation achieved by a continuous intravenous infusion of pentagastrin. The inhibition persisted during perfusion of the stomach with alkaline buffer. The plasma somatostatin concentration did not increase during distension and no somatostatin was detected in the gastric contents. Balloon distension of the antrum during laparotomy did not affect the concentration of somatostatin and gastrin in portal blood in patients with gallbladder disease or duodenal ulcer. The results confirm that antral distension stimulates acid secretion in duodenal ulcer patients without involvement of the gastrin mechanism. Moreover, the inhibition of acid secretion by antral distension in healthy subjects is independent of luminal pH and does not appear to be mediated by somatostatin.

Fat inhibition of gastric acid secretion in duodenal ulcer patients before and after proximal gastric vagotomy.

In seven duodenal ulcer patients the effect of intraduodenal infusion of 20 ml oleic acid on submaximal gastric acid secretion stimulation by a continuous pentagastrin infusion was evaluated before and after proximal gastric vagotomy. In the control tests 20 ml of saline was given. Before vagotomy, oleic acid evoked a significant inhibition of gastric acid secretion of 25% compared with the controls. This inhibition was abolished after proximal gastric vagotomy. The difference in inhibition before and after vagotomy was significant (P=0.01). It is concluded that the vagus nerve in man plays a decisive role in duodenal fat inhibition of gastric acid secretion.

Effect of sham feeding on gastric acid secretion in healthy subjects and duodenal ulcer patients: Evidence for increased basal vagal tone in some ulcer patients

Sham feeding augments gastric acid secretion by activating efferent vagal pathways to the stomach. If increased vagal activity in the basal state were the cause of increased basal acid secretion in some patients with duodenal ulcer, these patients might be expected to secrete little or no additional acid in response to sham feeding. To test this, we measured basal and sham feeding-stimulated acid secretion (as well as peak pentagastrin-stimulated acid output) in 29 duodenal ulcer patients and 22 healthy subjects. Four ulcer patients who had markedly increased basal acid secretion (basal/peak acid output > 0.30) and normal basal serum gastrin concentrations failed to augment acid secretion in response to sham feeding. On the other hand, patients with marked basal acid hypersection owing to hypergastrinemia (Zollinger-Ellison syndrome) responded to sham feeding with a large increase in acid secretion above basal rates. Every normal subject responded to sham feeding with an increase in acid secretion above basal rates, even when acid secretion had been stimulated by an intravenous pentagastrin infusion before beginning sham feeding. These findings suggest that in some patients with duodenal ulcer (4 of 29 in this study) increased basal acid secretion is caused by increased vagal tone.

Effect of an intravenous fat preparation on canine gastric secretion

The effect of intravenous administration of a fat emulsion on canine gastric secretion stimulated by intravenous infusion of amino acids, pentagastrin or insulin was studied. The fat preparation was given at a rate of 30 ml/hour for 2 hours, and its effects were compared with those of a comparable amount of saline solution, each given on three separate occasions in each dog. Fat did not alter the Heidenhain pouch secretion stimulated by intravenous amino acids (1.10 versus 1.11 mmol of hydrogen ion, p >0.9) or the gastrostomy secretion stimulated by intravenous insulin (9.22 versus 9.54 mmol of hydrogen ion, p >0.7) but had a modest inhibitory effect on Heidenhain pouch secretion stimulated by pentagastrin (2.75 versus 3.54 mmol of hydrogen ion, p <0.05). These data provide indirect support for the contention that the inhibition of gastric secretion by fat in the gut is mediated by the release of an enterogastrone rather than by a direct effect of absorbed fat. Because gastric stimulation by intravenous fat was not observed in the dog, it seems likely that intravenous fat emulsion can be given to seriously ill patients without fear of an increased likelihood of peptic ulceration due to induced gastric hypersecretion.