Effect Of Pentagastrin Research Articles

Stimulatory effect of pentagastrin on growth hormone and prolactin secretion in normal subjects.

Gastrin-like immunoreactive substances have been reported as occurring in both digestive tract tissues and nervous system, including the hypothalamus and the anterior and posterior pituitary. The carboxyterminal tetrapeptide shared by gastrin and cholecystokinin, which represents the bioactive site of both hormones, has been shown to be a secretagogue for insulin and glucagon and it might have a neurotrasmitter function. As small gastrin-like peptides may also play a role in the regulation of anterior pituitary hormones, the present study deals with the in vivo effect of pentagastrin on the release of growth hormone (GH) and prolactin (PRL). Six healthy volunteer males and six healthy volunteer females were studied. All females subjects were in the early follicular phase of the normal menstrual cycle and all subjects were not taking or had been taking any drug known to affect GH or PRL secretion. A continuous intravenous infusion of pentagastrin (1.5 micrograms/kg/h) was administered to all the subjects for a time of 3 hours. In males pentagastrin infusion resulted in a significant increase in GH concentration from basal values (P less than 0.01 at 60 min). In females pentagastrin infusion did not affect GH levels. PRL levels were not affected at all by intravenous pentagastrin infusion both in males and females. The exact understanding of pentagastrin action on GH release awaits further investigation. The different pattern between male and female subjects suggests a sexual hormone influence on the hypothalamic-pituitary sites of action of pentagastrin in vivo. Our data did not confirm a stimulatory effect of pentagastrin on PRL secretion in normal subjects.

Effects of pentagastrin and IGF-1 on DNA synthesis of rumen epithelial cells of dairy cow and neonatal calf

Effects of pentagastrin and IGF-1 on DNA synthesis of rumen epithelial cells of dairy cow and neonatal calf

The effect of a cholecystokinin agonist on masseter muscle activity in the cat.

The CCK(B) agonist, pentagastrin, has been shown to induce anxiety in human subjects. Similarly, in the cat model, pentagastrin facilitates the expression of hypothalamically activated emotional behavior. Because hypothalamically mediated emotional behavior is also accompanied by increased EMG activity in the jaw muscles, these experiments were designed to examine the combined effects of administration of pentagastrin with activation of hypothalamically mediated emotional behavior upon jaw muscle EMG activity. Electrodes were carefully lowered through previously placed guide tubes overlying the hypothalamus until a behavioral site was identified. Following the establishment of a stable threshold current for eliciting an emotional behavioral response, the skin overlying the ipsilateral masseter muscle was shaved and cleaned with alcohol, and surface electrodes were attached. The EMG was recorded, amplified, digitized, and stored in a microcomputer for analysis. Mean power frequencies (MPF) and latencies for behavior were calculated for baseline prior to infusion of all drugs. Following this, the effects of intravenous administration of pentagastrin and the CCK(B) antagonist LY288513 on the MPF were determined. The infusion of the CCK(B) agonist, pentagastrin (0.77, 1.92, and 3.84 microg/kg), decreased MPF in a time-related manner. The effects of pentagastrin 1.92 microg/kg were blocked by the CCK(B) antagonist, LY288513 (6.54 microg/kg). In addition, the infusion of LY288513 alone increased MPF. These results are surprising in that pentagastrin's anxiogenic properties would appear to make it likely to facilitate motor activity, not suppress it.

Effect of pentagastrin on IL-1β induced inhibition of insulin secretion in neonatal rat islets of Langerhans

Effect of pentagastrin on IL-1β induced inhibition of insulin secretion in neonatal rat islets of Langerhans

Developmental regulation of gastric somatostatin secretion in the sheep.

Gastric somatostatin (SRIF) regulates gastric acidity by inhibiting gastric acid and gastrin secretion. SRIF secretion is increased by gastric acidity and also directly by regulators of gastric acid secretion such as gastrin. This direct effect has not been described in the developing animal, nor have the roles of intermediaries such as histamine and gastric acidity been defined. The present study aimed to establish the regulatory role of gastrin and histamine during development on SRIF secretion and also to determine whether the effects of gastrin and histamine are independent of gastric pH. Pentagastrin and histamine were infused on separate occasions into fetal sheep, newborn lambs, and 28-day-old lambs. To determine the roles of endogenous histamine and gastric pH, ranitidine (a histamine-2 receptor antagonist) and omeprazole (a H+/K+ ATPase inhibitor) were coinfused with the agonists. Plasma SRIF and gastrin concentrations were measured by RIA. Pentagastrin stimulated SRIF secretion in the fetus after 131 days of gestation (term is 147 days), whereas stimulation by histamine was effective only after birth. The SRIF stimulatory effect of pentagastrin in 28-day-old lambs was abolished by ranitidine, which also reduced this effect in the adult sheep. This inhibitory effect of ranitidine was shown to be a result of blockade of stimulatory H2 receptors, because in the adult blockade of acid secretion with omeprazole failed to attenuate the response of histamine. These results indicate that in the fetus, gastrin receptors, but not histamine receptors, are functionally involved in the stimulation of SRIF secretion. After birth, both gastrin and histamine stimulate SRIF, but the effect of gastrin is mediated at least in part by the release of endogenous histamine. These responses occur independently of changes in gastric acidity, supporting the concept of a direct negative feedback between SRIF and gastrin.

Gastrin Stimulates Histamine Release from the Isolated Pig Stomach

Background: Gastrin has been shown to give an immediate and dose-dependent histamine release preceding acid secretion in the totally isolated, vascularly perfused rat stomach. Methods: In the present study we prepared isolated, vascularly perfused stomachs taken from pigs and examined the effect of pentagastrin in a concentration of 520 pM on the histamine release to the vascular bed. Pentagastrin was given for three 5-min periods at 10-min intervals, and histamine was determined by a radioimmunoassay method. Results: Each pentagastrin dose resulted in stimulation of histamine release in the three pig stomachs examined. The various histamine concentrations increased to levels previously shown to stimulate aminopyrine accumulation in isolated pig parietal cells. Conclusion: The present study shows for the first time that gastrin induces histamine release to the vascular bed in the pig, as previously shown for the rat and dog.

Transient increase of blood histamine level induced by pentagastrin. Continuous monitoring by in vivo microdialysis.

Since few studies of (penta)gastrin-induced histamine release from the gastric mucosa into blood has been performed, an effect of pentagastrin on histamine level of rat blood was examined by using the in vivo microdialysis method. Pentagastrin was perfused through the microdialysis probe implanted into the jugular vein of urethane-anesthetized rats or in urethane-anesthetized, totally gastrectomized rats, and dialysis samples of blood were concurrently collected. Histidine decarboxylase (HDC) activities and histamine contents in the glandular stomach and gastric acid output after pentagastrin stimulation were also investigated. Pentagastrin induced a transient increase of blood histamine in a dose-dependent manner but failed to cause any increase of blood histamine in the totally gastrectomized rat. Pentagastrin also induced increases of the HDC activity in the glandular stomach and of the gastric acid output. The peak histamine level in blood occurred 40 min after pentagastrin perfusion, whereas the peak acid secretion occurred after 80-120 min and then leveled off. The transient increase of blood histamine induced by pentagastrin is attributable to the histamine released from enterochromaffin-like cells and could be monitored by using the in vivo microdialysis method.

Pentagastrin induced panic attacks: enhanced sensitivity in panic disorder patients

The effects of pentagastrin, a synthetic analogue of the cholecystokinin tetrapeptide (CCK4), were studied in 15 patients with panic disorder and 15 healthy controls. Three different intravenous dosages of pentagastrin (0.1, 0.3 and 0.6 microgram/kg) and saline were investigated. Subjects were randomly allocated to two of the four treatment groups and tested on two separate occasions, 1 week apart, using an unbalanced double-blind incomplete block design. The mean panic rate with pentagastrin was 55% (12/22) for patients and 5% (1/22) for controls. None of the subjects panicked with saline. The frequency of panic attacks between the three pentagastrin doses in patients was not different. One control subject had a panic-like attack at the highest dose of pentagastrin. These findings concur with previous studies on the panicogenic effect of CCK4 and pentagastrin and suggest a greater sensitivity for CCK receptor agonists in patients suffering from panic disorder than in healthy controls.

Gastric secretion of platelet activating factor and precursors in healthy humans: effect of pentagastrin.

The release of platelet activating factor (PAF-ACETHER or PAF) and its precursors in the gastric lumen was assessed in 13 normal subjects in basal condition and after stimulation by gastrin. Acid, pepsin, and sialic acid outputs were determined under the same conditions. Gastric juice was collected using a nasogastric tube after overnight fast in basal condition for 60 minutes, then under pentagastrin infusion (6 micrograms/kg/hr for 60 minutes). Platelet activating factor was detected at low concentration in 4/13 subjects under basal condition (mean (SEM) 1.2 (0.6) pg/hr) while high concentrations of lyso platelet activating factor (6.1 (1.8) microgram/hr) and of alkyl-acyl-glycerophosphocholine (AAGPC) (11.5 (3) micrograms/hr) were found in 13 and 11 subjects, respectively. Platelet activating factor was not detected during pentagastrin infusion, while lyso platelet activating factor and alkyl-acyl-glycerophosphocholine were detected in 13 and in 12 subjects, respectively. Compared with the basal condition these platelet activating factor precursors increased significantly (p < 0.001) going up to fivefold baseline (31.8 (6.8) micrograms/hr and 53 (9.3) micrograms/hr respectively) in response to pentagastrin. There was a positive correlation between platelet activating factor precursors and acid or pepsin output but not between platelet activating factor precursors and sialic acid. As sialic acid may be considered an index of mucus glycoprotein degradation, it seems that gastrin stimulation of gastric epithelial cells results in a concomittant secretion of platelet activating factor precursors, acid, and pepsin irrespective of mucus glycoprotein degradation.

Pharmacological analysis of pentagastrin-modulated behavior caused by stimulation of the ventromedial hypothalamus

The purpose of the present investigations was to examine the neurochemical mechanisms of modulatory effect of pentagastrin (PG) on escape reaction elicited by the threshold electrical stimulation of the ventromedial hypothalamus (VMH) in rabbits. PG administration (35 mcg/kg intraventricularly) was found to transform escape into feeding. This phenomenon was shown to begin at 20 min and to last to 150 min after PG injection. The animals were treated with various antagonists to some classic neurotransmitters of the central nervous system. Kalipsol (0.25, 0.5 mg/kg intravenously) and ketanserin (0.1 mg/kg intravenously) were found to restore feeding into escape. GABA-ergic antagonist baclofen (0.25, 0.5 mg/kg) was demonstrated to shorten to about 30 min the time of feeding after PG administration. Both inderal-beta-adreno-blocker (0.25, 0.5, 1.0 mg/kg) and M-choline antagonist atropine (0.25, 0.5 mg/kg) were found to be ineffective in escape restoration in response to VMH stimulation. The experimental results suggest the important role of N-cholinergic and serotoninergic brain structures in PG transformation of escape elicited from the VMH into feeding.

Gastrin and the growth of the gastrointestinal tract

While the proliferative effects of gastrin in the gastric fundus are well established, there is a considerable degree of confusion regarding the role of gastrin on the growth of the small intestine and colon. The hypothesis that gastrin is trophic throughout the gut was tested by giving three doses of pentagastrin and one of gastrin 17 to rats maintained by total parenteral nutrition (TPN). The rats were fed intravenously for one week, with the various peptides added to the TPN diet. The number of vincristine arrested metaphases per gland or crypt was then scored to determine the proliferative state. Both gastrin 17 and pentagastrin were found to be trophic in the gastric fundus, but not to the gastric antrum. A proliferative response was also seen in the duodenum, but with little evidence of a dose response element. No effect on small bowel weight was seen, and no proliferative effect was noted in the mid small bowel, thus the duodenal effect could be attributed to a local action of increased acid output on the duodenum, not a general role throughout the small intestine. No proliferative effects of pentagastrin or gastrin were seen in the colon. It is therefore concluded that the trophic role of gastrin is restricted to the gastric fundus and the proximal duodenum.

Evidence for enhanced sensitivity for pentagastrin in panic disorder patients

SummaryWe studied the effects of pentagastrin, an analogue of the cholecystokinin tetrapeptide (CCK4), in 15 patients with panic disorder and 15 healthy controls. Three different intravenous dosages of pentagastrin (0.1, 0.3 and 0.6 μ/kg) and placebo (saline) were investigated. Subjects were randomly allocated to two of the four dosage groups and tested on two separate occasions, one week apart, using a double-blind incomplete block design. A total of 59 intravenous injections were carried out. The panic rate with pentagastrin, irrespective of the dosage, was 55% (12/22) for patients and 5% (1/22) for controls. None of the subjects panicked with saline. The frequency of panic attacks between the three pentagastrin doses in patients was not different. One control subject had a panic-like attack at the highest dose of pentagastrin. These findings concur with previous studies on the panicogenic effect of CCK4 and pentagastrin and suggest a greater sensitivity for CCK agonists in patients suffering from panic disorder than in healthy controls.

Unexpected effect of pentagastrin and its use in allogeneic organ grafting

Unexpected effect of pentagastrin and its use in allogeneic organ grafting

Effect of gastric stimulants on histamine release and circulatory responses

The effects of pentagastrin (6 μg/kg/h) or insulin (0.15 U/kg/h) on histamine release and blood circulation in nine anaesthetized dogs were studied by measuring (1) plasma histamine concentrations in the iliac artery, iliac vein, hepatic vein and portal vein, (2) the corresponding blood pressures, and (3) blood flow in the hepatic artery and the portal vein. In the portal vein, pentagastrin induced an overall 204% rise (p<0.01) in plasma histamine and a 28% rise (p<0.01) in blood flow while other measurements did not change significantly. Insulin did not induce similar rises. Three patients with duodenal ulcer (DU) undergoing proximal gastric vagotomy (PGV) were given pentagastrin (6 μg/kg) by bolus injection. Plasma histamine concentrations in the gastric veins draining the oxyntic cell area rose by 68%, 15 min after injection. Thus, specific histamine release may act as a mediator for pentagastrin-stimulated gastric acid secretion and as a vasodilator to facilitate gastric circulation. Insulin did not promote histamine release in the present study.

Pentagastrin Stimulates Potassium Absorption from the Rat Colon

Pentagastrin is trophic to the colon but the physiologic effects of pentagastrin are incompletely known. We compared in vivo potassium (K+) absorption from the colons of pentagastrin-treated (PG, n = 13), sham (S, n = 12), and control (C, n = 3) Sprague-Dawley rats during continuous intraluminal K+ perfusion. Preoperative intraperitoneal injections were administered to PG (pentagastrin 0.25 mg/kg in 2 mL 0.9% NaCl q 12 h x 48 h) and S (2 mL 0.9% NaCl q 12 h x 48 h). Under xylazine anesthesia, cannulae were placed in the cecum, rectum, and femoral artery of each rat. Intraluminal perfusion was performed for 2 h at 30 mL/min with 40 meq/L KCl in 0.9% NaCl (PG and S) or 0.9% NaCl (C). We monitored serum sodium (Na+) and K+ every 15 min, and the affluent and effluent Na+ and K+ every 30 min. At each interval past 60 min, we observed higher serum K+ in PG compared with S and C (P less than .002) and higher K+ in S compared with C (P less than .05). No changes in serum Na+ occurred. We conclude that pentagastrin stimulates potassium absorption from the colon.

Development of Acid Secretory Function in the Rat Stomach

Summary:Gastric acid secretion was studied in anesthetized rats from day 6 of the postnatal period up to the time of weaning. Basal H+ secretion was detected from day 6 in the first group studied (2.4 ± 0.2 μEq of H+/10 min/100 g of bodyweight, BW) and remained constant up to the time of weaning (day 18: 2.5 ± 0.2 μEq of H+/10 min/100 g of body weight) except for the period between days 10 and 12, when it fell significantly (1.5 ± 0.06 μEq H+/10 min/100 g of BW on day 12). Both histamine H2 receptor sensitivity and intracellular transduction mechanism activities were evaluated by studying the secretory responses to histamine, impromidine (an H2 receptor agonist), cimetidine (an H2 receptor antagonist), forskolin (a direct adenylate cyclase activator), and dibutyryl (db) cAMP (an analogue of cAMP, the intracellular messenger mediating the response to histamine). The effects of pentagastrin and carbachol were also determined. The secretory responses obtained on days 6, 8, and 18 were similar and represented about threefold increases over basal secretion for all the secretagogues used. After weaning on day 20, both the basal secretion and the response to secretagogues were significantly increased compared with those of unweaned animals. On day 12, the responses were always weaker than on both days 8 and 18. Injection of 1 mg/kg of corticosterone 21 acetate daily from day 8 resulted on day 12 in a basal secretion and a response to histamine equivalent to those measured in 18‐day‐old pups not injected. The results described in this article represent a potentially useful set of baseline data concerning the development of gastric acid secretion in the rat stomach. They reinforce the finding previously established in our laboratory that there is a regression of secretory activity on days 10‐12 of life in the rat.

Development of Acid Secretory Function in the Rat Stomach

Gastric acid secretion was studied in anesthetized rats from day 6 of the postnatal period up to the time of weaning. Basal H+ secretion was detected from day 6 in the first group studied (2.4 +/- 0.2 muEq of H+/10 min/100 g of body weight, BW) and remained constant up to the time of weaning (day 18: 2.5 +/- 0.2 muEq of H+/10 min/100 g of body weight) except for the period between days 10 and 12, when it fell significantly (1.5 +/- 0.06 muEq H+/10 min/100 g of BW on day 12). Both histamine H2 receptor sensitivity and intracellular transduction mechanism activities were evaluated by studying the secretory responses to histamine, impromidine (an H2 receptor agonist), cimetidine (an H2 receptor antagonist), forskolin (a direct adenylate cyclase activator), and dibutyryl (db) cAMP (an analogue of cAMP, the intracellular messenger mediating the response to histamine). The effects of pentagastrin and carbachol were also determined. The secretory responses obtained on days 6, 8, and 18 were similar and represented about threefold increases over basal secretion for all the secretagogues used. After weaning on day 20, both the basal secretion and the response to secretagogues were significantly increased compared with those of unweaned animals. On day 12, the responses were always weaker than on both days 8 and 18. Injection of 1 mg/kg of corticosterone 21 acetate daily from day 8 resulted on day 12 in a basal secretion and a response to histamine equivalent to those measured in 18-day-old pups not injected.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of pentagastrin and cimetidine on gastric blood flow measured by laser Doppler flowmetry.

Endoscopic laser Doppler flowmetry has been used to study the effect of the secretagogue pentagastrin and the H2-receptor antagonist cimetidine on gastric blood flow in 24 healthy subjects. The subcutaneous injection of pentagastrin, 0.6 micrograms/kg body weight, caused a significant increase in gastric acid secretion. This increase did not provoke any significant change in gastric blood flow, measured in seven defined areas of the oesophagus and stomach. Furthermore, no significant correlation was found between the level of basal and maximal acid secretion and blood flow. The infusion of 200 mg cimetidine caused a significant reduction of gastric blood flow in five of the seven investigated areas (P less than 0.05 and P less than 0.01). Cimetidine had no effect on blood pressure or skin blood flow, measured by laser Doppler flowmetry. The study was performed without previous stimulation of acid secretion, and blood flow reduction was measured in both the corpus and the antrum of the stomach. The effect of cimetidine is therefore hardly a result of the acid-reducing effect of the drug. In this study no significant relationship could be shown between the gastric wall blood flow and acid secretion.

Gastric secretion during aging in pyloric-ligated rats and effects of pentagastrin

Changes in basal- and pentagastrin-stimulated gastric acid, pepsin secretion as well as gastric mucosal histidine decarboxylase activity were examined in 4- to 21-month-old pyloric ligated Fischer-344 rats. In addition, serum gastrin levels, gastric mucosal DNA, and RNA content were determined in these rats. The results revealed that whereas acid secretion decreased progressively with age, pepsin output increased between 4 and 14 months of age and then decreased sharply. Serum gastrin levels decreased progressively with age, and 3 h of pyloric obstruction produced no apparent change in serum gastrin levels in any of the age groups. Gastric mucosal weight, DNA, and RNA content in 4-month-old rats were not significantly different from those of 14-month-old animals. However, in 21-month-old rats, each of these values were found to be significantly lower than in their 4- or 14-month-old counterparts. A single injection of pentagastrin (250 μg/kg) significantly stimulated acid and pepsin secretion (45–52%) in 4-month-old rats, but not in 14- and 21-month-old animals, when compared with the corresponding saline-injected controls. Gastric mucosal histidine decarboxylase activity increased steadily between 4 and 21 months of age. Pentagastrin caused a significant 78% stimulation in histidine decarboxylase activity in 4-month-old rats, but had no effect on the enzyme activity in 14-month-old animals, when compared with the corresponding saline-injected controls. However, in 21-month-old rats, pentagastrin inhibited histidine decarboxylase activity by 55% when compared with the saline-injected controls. It is concluded that a) aging decreases capacity of the gastric mucosa to secrete acid and pepsin, b) in aged rats, decreased acid and pepsin output could in part be attributed to mucosal atrophy; c) responsiveness of the gastric mucosa to pentagastrin decreases with age; and d) in aged animals, gastric acid secretion is not regulated by histamine.

Distinct activation of Na+-H+ exchange by gastrin and CCK peptide in acini from guinea pig

The effect of cholecystokinin (CCK)-gastrin family peptides (caerulein, unsulfated gastrin-17, and pentagastrin) and secretin in activating amiloride-sensitive 22Na uptake were investigated in guinea pig pancreatic acini. Secretin had no effect, but CCK-gastrin peptides stimulated the amiloride-sensitive 22Na uptake. The effect of caerulein was inhibited by dibutyryl guanosine 3',5'-cyclic monophosphate (cGMP) and asperlicin, indicating that activation of the Na+-H+ antiport caused by caerulein is mediated by CCK receptors. The effect of gastrin was dibutyryl cGMP and asperlicin insensitive, whereas the effect of pentagastrin was inhibited by the CCK antagonists but with a low affinity, indicating that the effect of gastrin and that of pentagastrin was CCK receptor independent. The calcium ionophore A23187 caused an increase in amiloride-sensitive 22Na uptake. However, the effect of caerulein, which increased internal calcium concentration, was not modified after depletion of intracellular calcium, and that of CCK-gastrin family peptides was not dependent on external calcium concentration. Activation of amiloride-sensitive 22Na uptake was also induced by 12-O-tetradecanoylphorbol 13-acetate and 1-oleoyl-2-acetyl-glycerol. Activation of protein kinase c may be involved in the mechanism of caerulein or gastrin in activating the Na+-H+ exchange.