Effect Of Pentagastrin Research Articles

Effects of pentagastrin and carbachol on the gastric histamine level in alpha-fluoromethylhistidine-treated mice and rats.

The gastric mucosal histamine level in mice increased by about 80% and 100% after fasting for 24 and 48 h, respectively. In non-fasted mice, alpha-fluoromethylhistidine (alpha-FMH), a specific histidine decarboxylase inhibitor, significantly decreased the histamine level, the reduction amounting to 35% and 49%, 2 h and 4 h after treatment, respectively. In mice fasted for 24 h, a significant decrease of 42% was observed 4 h after treatment. However, in mice fasted for 48 h, no significant decrease was seen even 4 h after alpha-FMH treatment. Therefore, the histamine-releasing effect of re-feeding and drugs on the gastric mucosa was examined in vivo, using animals fasted for 48 h and subsequently treated with alpha-FMH. Food given simultaneously with alpha-FMH to 48-h fasted mice significantly decreased the histamine level 4 h later. Pentagastrin and carbachol administered alone (0.25-2.0 mg/kg, i.p.) had no significant effect on the histamine level. However, the combined treatment with these drugs significantly decreased the histamine level. In rats fasted for 48 h and treated with alpha-FMH, pentagastrin (0.25 and 0.5 mg/kg, i.p.) but not carbachol (0.125-0.5 mg/kg, i.p.) caused a significant decrease in the mucosal histamine level. In contrast to mice, the effect of the combined treatment with pentagastrin and carbachol was not synergistic in rats. These findings suggest that gastrin acts synergistically with acetylcholine in the histamine release from the gastric mucosa in mice, whereas such synergism may not occur in rats.

Adrenalectomy and pentagastrin effects on gastrointestinal cholinergic enzyme activities.

The present study examined the effects of pentagastrin and adrenalectomy on choline acetyltransferase (ChAT) and acetylcholine esterase (AChE), enzymes which synthesize and degrade acetylcholine in the rat gastrointestinal tract. Adrenalectomized and non-adrenalectomized rats, 14 and 21 days old, were treated with either pentagastrin (250 micrograms/kg i.p.) or saline for 7 days. Rats were sacrificed at 21 and 28 days of age. Adrenalectomy- and pentagastrin-treated 21-day-old rats had greater ChAT activities than those treated with pentagastrin alone, while AChE activities were higher in the pentagastrin-treated group. Adrenalectomy- and pentagastrin-treated 28-day-old rats had lower levels of activity as compared to pentagastrin-treated rats. The adrenal gland does appear to influence the response of cholinergic enzyme activities to pentagastrin.

Effect of pentagastrin on cell proliferation in DMH-induced adenocarcinoma in rats

Effect of pentagastrin on cell proliferation in DMH-induced adenocarcinoma in rats

Effect of pentagastrin, secretin and cholecystokinin on growth and differentiation in organ cultured rabbit small intestine.

The effect of pentagastrin, secretin and cholecystokinin on biochemical parameters of mucosal growth and differentiation was studied in organ cultured rabbit jejunum and ileum. Pentagastrin at 0.05-5.0 microgram/ml did not affect DNA content of the biopsy, but led to a significant decrease of sucrase and alkaline phosphatase activity in the ileum. Secretin prompted a significant decrease of DNA and protein in the ileum at a level of 10(-7) and 10(-5) M, but had no effect in the jejunum. Of the brush border enzymes, sucrase and alkaline phosphatase were suppressed in both parts of the intestine both with respect to specific activity and total biopsy content. Cholecystokinin, like pentagastrin, did not influence DNA or protein content, but reduced sucrase, maltase and alkaline phosphatase activity. HMG-CoA reductase, the key enzyme of cholesterol synthesis, was not significantly affected by any of the three hormones tested. When brush border enzymes or DNA from desquamated cells were measured in the post-culture medium, no consistent effect of any gastrointestinal hormone was apparent. The present study demonstrates a direct "antitrophic" effect of secretin in cultured mucosa. Pentagastrin and cholecystokinin did not influence mucosal DNA content in vitro but apparently inhibited villus cell differentiation.

Pentagastrin and gastric mucosal blood flow.

The effect of pentagastrin on mucosal microcirculation was studied in rats by use of intravital microscopy. The superficial mucosal vessels were videorecorded for off-line analysis of red cell velocities (VRBC) and vessel diameters, from which blood flow (QRBC) was calculated. Resting mucosal blood flow calculated from single microvascular flow data, and vessel distribution was 40 ml X min-1 X 100 g-1. Pentagastrin infused intravenously in a dose of 20 micrograms X kg-1 X h-1 resulted in submaximal acid secretion (approximately 60%) and a significant increase in QRBC by 47 +/- 14%. When given in a dose of 96 micrograms X kg-1 X h-1 iv, it resulted in maximal acid secretion and an increase in QRBC by 36 +/- 14%. In another series of experiments the results of QRBC measurements during infusion of pentagastrin (20 micrograms X kg-1 X h-1 iv) were compared with those of aminopyrine (AP) clearance or laser-Doppler flowmetry (LDF) in the same animals. Gastric mucosal blood flow determined by [14C]AP clearance increased by 309 +/- 115%, whereas QRBC increased by 34 +/- 11%. When determined by LDF, blood flow increased by 41 +/- 22%, a value similar to the increase in QRBC (50 +/- 19%). Thus, the percent increase in blood flow during pentagastrin infusion estimated by AP clearance was considerably higher than that observed by either direct microvascular measurements or by LDF.

Effect of Pentagastrin on Gastric Acid Secretion in the Totally Isolated Vascularly Perfused Rat Stomach Stimulated with the Phosphodiesterase Inhibitor Isobutyl Methylxanthine

The development of a very sensitive stomach biomodel, using the totally isolated rat stomach, is reported. Pentagastrin-stimulated acid secretion in anesthetized and conscious rats was also studied, and the capacity to produce acid and the sensitivity towards pentagastrin in the different rat stomach models were compared. The secretory capacity and the sensitivity were evaluated by means of the maximal acid output (MAO) and threshold dose (TD), respectively. Conscious rats provided with gastric fistulas had a MAO of 48 +/- 6.3 mu eq/10 min and a TD of 6 micrograms/kg-h. In anesthetized rats with luminally perfused stomach MAO was reduced to 11.6 +/- 1.2 mu eq/10 min, whereas the sensitivity was increased, as indicated by a TD of 0.5 micrograms/kg-h. Totally isolated vascularly perfused rat stomachs without isobutyl methylxanthine (IMX) produced even less acid (MAO, 2.2 +/- 0.4 mu eq/10 min) without any change in demand for stimulant (TD, 0.25 micrograms/stomach-h). Addition of IMX to the vascular perfusate in the isolated stomach preparation increased the MAO to 8.0 +/- 1.0 mu eq/10 min and induced a remarkable reduction in demand for stimulant, with a TD obtained already at a pentagastrin dose of 0.008 micrograms/stomach-h, corresponding to a concentration of pentagastrin in the vascular perfusate medium of 84.5 pM. Accordingly, the totally isolated vascularly perfused rat stomach stimulated with IMX is the most sensitive bioassay for (penta)gastrin so far reported.

The effect of pentagastrin on the gastric secretion by the totally isolated vascularly perfused rat stomach.

Gastric acid and pepsin secretion by the totally isolated vascularly perfused rat stomach was studied. Rat stomachs were vascularly perfused with Krebs-Ringer buffer gassed with 96% O2-4% CO2 and containing 5 mM glucose, 5 mM pyruvate, 4% bovine serum albumin, 10% ovine erythrocytes, and various concentrations of pentagastrin. The gastric lumen was perfused with distilled water gassed with 100% O2. To remove preformed juice and to enable preformed pepsin to be washed out, the initial 20-min gastric juice was discarded. The gastric effluent was then collected continuously for six 10-min periods, and the H+ concentration was determined by titration and the pepsin concentration estimated by a hemoglobin digestion method. Inclusion of pentagastrin in the perfusion buffer increased the acid output dose-dependently from 2.3 +/- 0.4 mueq/h during the control perfusion to a maximum of 12.7 +/- 2.1 mueq/h (p less than 0.01). With the higher doses of pentagastrin and concomitant high acid secretion, gastric acid secretion faded during the collection period. In contrast, gastric pepsin secretion was virtually unaffected by pentagastrin. The present model should be useful for studying the regulation of gastric acid and pepsin secretion.

Comparative study of hydrogen and aminopyrine clearance methods for determination of gastric mucosal blood flow in dogs.

Effects of pentagastrin, histamine, PGI2, and vasopressin on gastric mucosal blood flow (GMBF) in innervated stomaches of anesthetized dogs were measured by means of the hydrogen clearance method, using a contact electrode. The results were compared with findings obtained with the aminopyrine (AP) clearance method in Heidenhain pouch preparations. Pentagastrin at 2 and 8 micrograms/kg/hr had no effects on GMBF, as measured by the hydrogen clearance method, but there was a marked increase in GMBF when the AP clearance method was used. Histamine at 40 or 160 micrograms/kg/hr tended to reduce or significantly reduced GMBF when measured with the hydrogen clearance method, but there was a significant increase in GMBF with the AP clearance method. Both PGI2 (3 or 30 micrograms/kg/hr) and vasopressin (0.06 or 0.25 units/kg/hr) reduced GMBF as determined by both methods. These results indicate that the hydrogen clearance method is advantageous for detecting regional GMBF but is disadvantageous when attempting to detect the effects of agents which increase GMBF.

Proglumide inhibition of trophic action of pentagastrin.

Proglumide, a glutaramic acid derivative, inhibits the acid secretory effects of gastrin and is said to be a specific gastrin receptor blocking agent. In the current study we have shown that proglumide inhibits the binding of gastrin to its receptor in rat oxyntic gland mucosa and tested whether this receptor is also responsible for the trophic effect of gastrin. In the first study 400 mg/kg proglumide injected with 250 micrograms/kg pentagastrin every 8 h for 48 h totally prevented the trophic effects of pentagastrin in rat oxyntic gland mucosa. Parameters measured included DNA synthesis and DNA, RNA, and protein content. In a second study the lowest maximally effective dose of proglumide was determined to be 100 mg/kg. The trophic effect of pentagastrin was inhibited in duodenal mucosa, colonic mucosa, and pancreas as well as oxyntic gland mucosa. These data demonstrate that proglumide blocks the trophic action of exogenous gastrin and suggest that the trophic effect of gastrin is mediated by the gastrin receptor.

Pentagastrin potentiates nonadrenergic inhibitory neuromuscular transmission in orad stomach of the dog.

Mechanical and intracellular electrical activities were recorded separately from circular muscle of the orad corpus of the canine stomach. In normal Krebs solution, transmural electrical nerve stimulation produced excitatory and inhibitory responses. The excitatory response was blocked by atropine; the inhibitory response was unaffected by phentolamine or propranolol alone or in combination. Both responses were blocked by tetrodotoxin. In the presence of pentagastrin, the inhibitory response to electrical nerve stimulation was potentiated in a dose-dependent manner. The threshold concentration for this potentiating effect was 3 X 10(-11) M. Intracellular recordings showed that hyperpolarization of the resting membrane potential in response to inhibitory nerve stimulation was greater in the presence of pentagastrin than in its absence. These data suggest that, in addition to a direct stimulatory effect on the muscle, pentagastrin also potentiates the effect of ongoing activity of intramural inhibitory nerves. This latter effect is only apparent when the inhibitory neural network is active. Thus, the in vivo effect of pentagastrin on motor activity of the corpus will depend on the degree of ongoing activity of intramural inhibitory nerves.

Histamine Release From a Gastric Carcinoid: Provocation by Pentagastrin and Inhibition by Somatostatin

We have previously reported that flushing associated with a gastric carcinoid tumor can be provoked by pentagastrin and inhibited by either somatostatin or combined histamine H1- and H2-receptor blockade. In this report, the effects of pentagastrin and somatostatin on histamine release in a patient with a metastatic gastric carcinoid tumor were examined. Small doses of intravenous pentagastrin (0.1-0.4 micrograms) produced a dose-dependent increase in the level of circulating plasma histamine. Graded infusions of somatostatin suppressed both basal and pentagastrin-stimulated plasma histamine levels in a dose-dependent fashion. A close correlation was found between circulating plasma histamine levels and attendant changes in blood pressure and pulse rate. This study documents that pentagastrin directly evokes the release of histamine from this patient's gastric carcinoid tumor and that the release of histamine is inhibited by somatostatin. In addition, this study provides additional evidence that the primary mediator of the flushing in this patient with foregut carcinoid syndrome is histamine.

Comparative study of hydrogen and aminopyrine clearance methods for determination of gastric mucosal blood flow in dogs

The effects of pentagastrin, histamine, PGI2 and vasopressin on gastric mucosal blood flow (GMBF) in innervated stomachs of 8 anesthetized dogs (8-17 kg) were measured using the hydrogen clearance method.

Effect of pentagastrin on mouse gastric and small intestinal mucosa in vivo and in vitro

1. 1. Single administration of various doses (62.5, 125, 250, 500 μg/kg bodyweight) or multiple administration of a single dose (250 μg/kg body wt) of pentagastrin to fasted mice do not alter the protein and DNA content, nor the DNA synthesis in fundus of stomach, distal duodenum, and proximal jejunum. 2. 2. Pentagastrin has also been added at different doses into an organ culture of adult mouse duodenum or jejunum. 3. 3. The explants were taken from animals fasted for 24 or 48 hr before sacrifice. 4. 4. Protein and DNA content, protein and DNA synthesis, activities of several brush border enzymes and morphology have not been modified. 5. 5. Therefore, the drug does not seem to have a direct effect on the mouse intestinal mucosa. 6. 6. These observations are compared to results obtained from other species.

444 Effect of pentagastrin on the directional migration of colon cancer cells in vitro

444 Effect of pentagastrin on the directional migration of colon cancer cells in vitro

Effects of pentagastrin, histamine, carbamylcholine and catecholamines on gastric secretion, motility and emptying in the rat

We developed a simplified method for the simultaneous measurement of gastric secretion and gastric motility in the rat. By using this method, we investigated the actions of pentagastrin, histamine, carbamylcholine and catecholamines on the stomach. Carbamylcholine stimulated acid secretion and induced contraction of the stomach, but norepinephrine tended to inhibit acid secretion and induced relaxation of the stomach. Histamine induced relaxation first and then contraction after 2–5 min. Pentagastrin induced a relaxation that did not show dose dependence, but tachyphylaxis. Isoproterenol, which stimulated acid secretion in our experiments, induced relaxation of the stomach in a dose-dependent manner. We also investigated the relationship between gastric motility and gastric emptying. Carbamylcholine caused an enhancement of gastric emptying, but isoproterenol caused its suppression. Pentagastrin, histamine and norepinephrine did not affect gastric emptying. As shown in the results of our experiments, carbamylcholine caused stimulation of acid secretion, contraction of the stomach, and enhancement of gastric emptying. However, other secretagogues did not always induce contraction of the stomach or increase gastric emptying.

Ontogeny of gastric acid secretion in the rat: evidence for multiple response systems.

Gastric acid secretion has been thought to depend on histamine stimulation of the parietal cell. However, in the 2-week-old rat neither exogenous histamine nor the H-2 receptor agonist impromidine stimulates acid secretion, whereas pentagastrin and the cholinergic agent bethanechol are potent stimuli. At this age, the effect of pentagastrin in acid secretion is not blocked by the H-2 receptor antagonist cimetidine, nor is it potentiated by impromidine. These data suggest that, in the rat pup, the acid secretory response to pentagastrin and cholinergic agents occurs before the histamine-mediated system is functional and operates independently of the actions of histamine.

Interaction of glucagon and pentagastrin on pepsin secretion in healthy subjects.

The effect of pentagastrin in step-wise increasing doses of 0 . 02, 2 . 0 and 20 nmol/kg/h (0 . 01, 1 . 0, and 10 . 0 micrograms/kg/h) on pepsin and acid secretion was studied in seven healthy subjects. The study was repeated on another day during infusion of glucagon in a dose of 103 pmol/kg/h (0 . 36 micrograms/kg/h) which results in plasma-glucagon concentrations comparable with those seen after a protein-rich meal. Pepsin output was maximal after 0 . 2 nmol/kg/h (0 . 1 microgram/kg/h) of pentagastrin and 20 nmol/kg/h (10 micrograms/kg/h) resulted in a marked decrease. The dose of pentagastrin required for half-maximal pepsin output was less than 0 . 1 nmol/kg/h (0 . 05 micrograms/kg/h). When the study was repeated during infusion of glucagon, the dose-response curve was shifted to the right. The highest pepsin output was obtained with 20 nmol/kg/h (10 micrograms/kg/h) of pentagastrin and D50 increased to well over 1 microgram/kg/h. The dose of pentagastrin required for half-maximal acid secretion was about 0 . 3 nmol/kg/h (0 . 15 micrograms/kg/h) indicating that the sensitivity of the chief cells to pentagastrin is more than three times that of the parietal cells.

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.

Effect of vagotomy on gastric acid secretion in the rat

The effects of pentagastrin, histamine or feeding on gastric acid secretion were studied in conscious rats with total gastric by-pass, achieved by transection of the cardia and pylorus, followed by an oesophago-duodenostomy. After closure of the cardia, the by-passed stomach was connected to the small intestine through a Roux-en-Y loop. A chronic gastric fistula was fitted into the rumen. Basal acid output was low in chronically vagotomized rats, being 6% of that in the innervated animals. A clear-cut stimulation was observed after both pentagastrin and histamine in innervated as well as denervated rats, although the maximal acid output in the denervated group was less than 10% of that in the innervated group. In previous studies on acid secretion in vagotomized rats with chronic gastric fistulas, neither basal nor stimulated acid secretion could be detected. Apparently, by-passing the stomach eliminates sources of error associated with the conventional gastric fistula technique (for instance, neutralization of acid gastric juice by swallowed saliva or regurgitated duodenal juice). Nonetheless, the greatly reduced acid output following vagotomy indicates that normal basal as well as normal stimulated acid secretion is dependent upon an intact vagus. Pentagastrin- and histamine-stimulated acid secretion was blocked by atropine and cimetidine in both the innervated and denervated rats. Feeding caused a significant inhibition of acid secretion in the by-passed, innervated stomach. In the denervated stomach feeding was without effect. The mechanism behind the postprandial inhibition of acid secretion in the innervated stomach is obscure. Direct vagal inhibition as well as humoral substances, liberated by vagal stimulation or by the presence of food in the intestine, may be responsible.

Gastric mucosal cell proliferation during development in rats and effects of pentagastrin.

Changes in cell proliferation and cell loss in the gastric mucosa were examined during the first 4 wk of life. The effect of pentagastrin on these parameters before and after weaning was also investigated. The results revealed that DNA content of mucosa and lumen increased with age. However, when luminal DNA (an assessment of cell loss) content was expressed as percent of total mucosal DNA (referred to as percent cell loss), an inverse relationship with age was observed. The rate of mucosal DNA synthesis, measured in vitro, was found to remain elevated up to the age of 15 days and then dropped dramatically within the next 5--6 days after which it decreased slowly. The rate of mucosal DNA synthesis in 5- to 15-day-old rats was found to be 10--15 times higher than in 20- to 30-day-old rats. In 10-day-old suckling young, mucosal thymidine kinase activity was also found to be higher than in 20- to 28-day-old rats. On the other hand, total incorporation of [3H]thymidine into mucosal DNA per stomach was found to be significantly greater in 21- to 28-day-old weaned rats than in the 10-day-old suckling young. Multiple injections of pentagastrin to 28-day-old rats significantly increased mucosal DNA synthesis and thymidine kinase activity by 43 and 200%, respectively, and cell loss by 30% when compared with the saline control. The hormone did not affect DNA synthesis, thymidine kinase, or cell loss in 10-day-old rats. There were considerable increases in 20-day-old rats that were not statistically significant due to the variation of the data.