Intravenous Infusion 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.

The effect of gastric secretion on gastric physiology and emptying in the fasted and fed state assessed by magnetic resonance imaging

Conventional measurement of gastric secretion is invasive and cannot assess the intra-gastric distribution of gastric contents or the effects of secretion on gastric function. This study assessed the effect of gastric secretion on gastric volume responses and emptying (GE) using a validated fast T(1) mapping magnetic resonance imaging (MRI) technique. Twelve healthy participants were studied in the fasted state and after 200 kcal Gadolinium-DOTA labelled glucose meal during intravenous infusion of pentagastrin or placebo in double-blind, randomized order. Total gastric volume (TGV) and gastric content volume (GCV) was assessed by MRI volume scans and secretion by fast T(1) mapping. Data was described by the kappa-coefficient (volume change after meal ingestion), by GE half time (T(50)) and maximal GE rate (GER(max)) derived all from a GE model. Pentagastrin increased GCV and TGV compared to placebo [kappa(GCV):1.6 +/- 0.1 vs 0.6 +/- 0.1; kappa(TGV): 1.6 +/- 0.1 vs 0.7 +/- 0.1; P < 0.001]. T(1) maps revealed a secretion layer above the meal, the volume of which was associated with kappa (R(2) = 83%, P < 0.001). TGV and GCV change were similar in both conditions (kappa; P = ns). T(50) was higher for pentagastrin than for placebo (84 +/- 7 vs 56 +/- 4min, P < 0.001); however, GER(max) was similar (5.9 +/- 0.6 vs 4.9 +/- 0.4 mL min(-1), P = ns). This study shows volume and distribution of gastric secretion can be quantified in-vivo by non-invasive MRI T(1) mapping. Increased GCV drove TGV accommodation without evidence of a direct effect of pentagastrin or excess acid on gastric function. Secretion increases GCV thus prolongs GE as assessed by T(50); however, GE rate is unchanged.

Plasma ghrelin is increased following gastrin stimulation

Background: Ghrelin is primarily secreted from the gastric mucosa and has been shown to increase appetite and weight in humans. Plasma concentrations are increased pre-meals but reduced in the fed state. We therefore examined the effects of gastrin stimulation on peripheral plasma ghrelin concentrations in normal human subjects. Methods: Eight normal, H. pylori-negative volunteers (4 male; mean age 26.9 (21–54) years) were studied. Ethical approval for this study was granted by the Ethical Committee of Queen's University of Belfast. Each underwent basal and maximal acid secretory studies before, on completion, and 28 days following a 28-day course of the proton pump inhibitor, esomeprazole 40mg daily. For each acid secretory test, basal blood samples were collected 50 and 40 minutes prior to commencing a 60-minute intravenous infusion of pentagastrin (0.6µg/kg/hr) with further blood sampling at 45, 90 and 240 minutes after commencing the infusion. Plasma gastrin and ghrelin concentrations were assessed by radioimmunoassay. Statistical analysis employed the Wilcoxon Signed Ranks test. Results: Plasma ghrelin was increased by pentagastrin infusion before (p<0.01), on completion (p<0.05) and 28 days following (p<0.01) esomeprazole (165.2 to 220.1 pmol/l, 237.7 to 266.5 pmol/l, 181.9 to 201.0 pmol/l, respectively). The ghrelin increase occurred at 45min and remained elevated at 240min in all three studies. Mean basal plasma gastrin and ghrelin was also increased (25.0ng/l to 51.3 ng/l (p<0.05) and 165.2 pmol/l to 237.7 pmol/l (p<0.01) respectively) following 28 days of esomeprazole. By day-28 post-esomeprazole, both plasma gastrin and ghrelin concentrations had returned to pre-treatment values. Conclusions: Plasma ghrelin was significantly increased by infusion of pentagastrin at a dose inducing maximal gastric acid secretion. This increase occurs immediately and may imply linkage with ECL cell histamine release. Treatment with esomeprazole also causes a significant rise in plasma ghrelin probably by causing an endogenous hypergastrinaemia. This study demonstrates that gastrin plays a key role in ghrelin activity and release. It also demonstrates that the mode of cellular communication amongst oxyntic and antral endocrine cell types requires further examination and additional evaluation of pharmacological intervention is necessary. Acknowledgements: PM Lynch was supported by a United Hospitals Trust Clinical Research Fellowship.

Microinjection of bombesin into the ventrolateral reticular formation inhibits peripherally stimulated gastric acid secretion through spinal pathways in rats

Bombesin injected into the cisterna magna potently inhibits gastric acid secretion stimulated by intravenous infusion of pentagastrin. Sites in the medulla oblongata where bombesin acts to suppress gastric acid secretion were investigated in urethane-anesthetized rats with gastric cannula. Bombesin or vehicle was injected into the medullary parenchyma or intracisternally (i.c.) 60 min after the start of an intravenous pentagastrin infusion; gastric acid secretion was monitored every 10 min for 20 min before and 150 min after the start of pentagastrin. Bombesin (0.2, 0.6 or 6.2 pmol) microinjected into the ventrolateral reticular formation (VLRF) inhibited dose-dependently the net acid response to pentagastrin by 40.8±11.1, 75.4±12.8 and 96.7±19.4%, respectively, at the 40–50 min period after microinjection compared with the vehicle group. Bombesin action in the VLRF was long lasting (96% inhibition still observed at 90 min after 6.2 pmol), and completely abolished by cervical spinal cord transection at the C6 level. By contrast, bombesin injected i.c. at 0.2 or 0.6 pmol had no effect while at 6.2 pmol, there was a 79.0±3.9% peak inhibition of pentagastrin-stimulated acid secretion. Bombesin (6.2 pmol) injected into the dorsal motor nucleus reduced the acid response to pentagastrin by 29%. The parvicellular and gigantocellular reticular nuclei were not responsive to bombesin. These results indicate that bombesin acts in the VLRF to inhibit pentagastrin-stimulated gastric acid secretion through spinal pathways, suggesting a potential role of medullary VLRF area in the sympathetic control of gastric acid secretion.

Leptin secretion and leptin receptor in the human stomach

BACKGROUND AND AIMThe circulating peptide leptin produced by fat cells acts on central receptors to control food intake and body weight homeostasis. Contrary to initial reports, leptin expression has also...

Role of endogenous nitric oxide in duodenal bicarbonate response induced by mucosal acidification in rats: Interaction with prostaglandins

Background & Aim. The circulating peptide leptin produced by the fat cells, acts on central receptors to control food intake and body weight homeostasis. Contrary to initial reports, leptin expression has also been detected in the human placenta, the muscles and recently rat gastric chief cells. Here we investigate the possible presence of leptin and leptin receptor in human stomach. Methods. Immunohistochemistry, reverse transcriptase (RT-PCR) and western blot analysis on biopsy samples from 24 normal individuals was used to investigate leptin and leptin receptor expressions. These individuals were randomly selected from the files of our Gastroenterology Department. They included 15 healthy volunteers and 9 patients with non-ulcer dyspepsia (n=24) who gave informed consent for upper endoscopy and gastric secretory tests. Secretory studies upon pentagastrin (6J,Lg/kg/hr) or secretin (3Ul/kg.hr) infusions, available for 22 subjects (mean age 46.7::':: 3.lyears; range 15-67,9 women, l3 men) were analyzed. At the time of study, all had normal endoscopy and normal gastric mucosa on histological examination. Plasma, gastric juice and fundic mucosa leptin were determined by radioimmunoassay. Results. In fundic biopsies from normal individuals, immunoreactive leptin cells were found in the lower half of the fundic glands at the site of chief cells. mRNA encoding ob-protein was detected in the corpus of human stomach. The amount of fundic content of leptin was 10.4 ::':: 3.7 ng leptin/g mucosa as determined by radioimmunoassay. Intravenous infusions of pentagastrin or secretin caused an increase in circulating leptin levels and leptin release into the gastric juice from 24.5 ::'::.3.5 in basal condition to 109 ::':: 26 ng/h under pentagastrin and 1556 ::':: 107 ng/hr under secretin. Gel filtration of leptin incubated with stimulated gastric juice at pH 2 showed an only limited degradation of this peptide. Immunohistochemistry and immunoblotting detected leptin receptor protein and mRNA encoding Ob-RL in the corpus and the antrum. Conclusion. These data provide the first evidence for the presence of leptin and leptin receptors in human stomach. We suggest that gastric epithelial cells be direct targets of leptin. However, the physiological and/or pathophysiological meanings of these findings remain so far unknown.

Inhibition of sham feeding-stimulated acid secretion in dogs by immunoneutralization of gastrin.

A monoclonal antibody to gastrin was used to study the role of circulating gastrin in mediating acid secretion stimulated by sham feeding in dogs. On separate days, four conscious, fasted, adult mongrel dogs with esophageal and gastric fistulae were pretreated intravenously with either 7 mg of gastrin monoclonal antibody (MAb 28.2), 7 mg of keyhole limpet hemocyanin monoclonal antibody as control, or 12.5 micrograms/kg atropine sulfate. Thirty minutes later, acid secretion was stimulated first by sham feeding for 5 min, then, 60 min later, by an intravenous infusion of a maximum stimulatory dose of histamine (40 micrograms/kg) for 60 min, and after returning to basal, by intravenous infusion of a submaximal stimulatory dose of gastrin (200 pmol.kg-1.h-1) for 60 min. Acid output from secretions collected every 15 min by gravity drainage was determined by titration to pH 7.0 with 0.2 N NaOH. Sham feeding-stimulated acid output (17.7 +/- 5.5 mmol/h) was significantly inhibited by administration of either MAb 28.2 (0 mmol/h) or atropine (1.7 +/- 1.1 mmol/h). Histamine-stimulated acid output (19.6 +/- 3.4 mmol/h) was not reduced by either pretreatment. Gastrin-stimulated acid output (3.9 +/- 0.6 mmol/h) was significantly reduced only by pretreatment with MAb 28.2 (0.1 +/- 0.1 mmol/h) and not by atropine (2.2 +/- 1.4 mmol/h). A background intravenous infusion of pentagastrin (0.5 microgram.kg-1.h-1) restored sham feeding-stimulated acid output blocked by administration of MAb 28.2, although the intrinsic acid response to sham feeding could not be seen with the background pentagastrin infusion. Furthermore, the plasma gastrin response to sham feeding was not blocked by atropine pretreatment. Because immunoneutralization of both gastrin and cholinergic blockade significantly inhibited acid output during sham feeding, circulating gastrin and cholinergic pathways are involved in mediating the cephalic phase of gastric acid secretion in dogs.

Nitric oxide, prostaglandin, and sensory neurons in gastric mucosal blood flow response during acid secretion in rats

1. 1. The mechanism underlying the increase of gastric mucosal blood flow (GMBF) during acid secretion induced by pentagastrin was investigated in anesthetized rats, in relation to nitric oxide (NO), prostaglandin (PG), and sensory neurons. 2. 2. An intravenous infusion of pentagastrin at 60 μg/kg/h (submaximal dose) produced an increase of acid secretion and GMBF as determined by laser Doppler flowmetry, and the GMBF response was totally attenuated when the acid secretion was inhibited by omeprazole or when the luminal H + was removed by mucosal perfusion with glycine (200 mM). 3. 3. Prior administration of N G-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg, IV), a NO synthase inhibitor, significantly mitigated the GMBF response to pentagastrin, without any influence on acid secretion, and this effect was antagonized by coadministration of L-arginine (500 mg/kg IP). 4. 4. The increase of GMBF during pentagastrin infusion also was significantly mitigated by indomethacin (5 mg/kg, SC) or sensory deafferentation following capsaicin pretreatment, had no effect on the acid secretion, and was totally inhibited by the combined treatments with indomethacin plus L-NAME in addition to sensory deafferentation. 5. 5. Pentagastrin infusion for 8 hr did not by itself cause any macroscopic damage in the stomach, but additional treatments with L-NAME, and indomethacin plus sensory deafferentation provoked severe lesions in the gastric mucosa. 6. 6. These results suggest that the increase of GMBF induced by submaximal dose of pentagastrin totally depends on luminal H +. This process seems to be mediated by endogenous NO and PGs, as well as capsaicin-sensitive sensory neurons, and to play a pivotal role in maintaining mucosal integrity during acid secretion.

The effect of ethanol, beer, and wine on histamine release from the dog stomach

The mediator for the action of ethanol on the parietal cell of the stomach is not known. However, because the action the ethanol on gastric acid secretion was proposed to involve the release of histamine, we decided to investigate the effects of ethanol and some alcoholic beverages (red wine and beer) on histamine release from the dog stomach. After performing a splenectomy in anaesthetized beagle dogs, the gastrosplenic vein draining the corpus of the stomach was cannulated for blood withdrawal to evaluate the local release of gastrin and histamine by RIA. Intragastric administration of 200 ml of beer (4.8% ethanol) or red wine (12.5% ethanol) caused a significant enhancement in gastric and histamine concentrations in venous blood from the stomach. By contrast, intragastric administration of pure ethanol in distilled water at the same concentrations of wine or beer did not significantly modify gastrin and histamine release. Integrated histamine responses for 20 min to beer and wine paralleled gastrin concentrations and were of the same magnitude of those induced by intravenous infusion of pentagastrin at 1 and 6 μg/kg/h, respectively. We conclude that: 1) beer and red wine, but not pure ethanol, are potent releasers of histamine; 2) histamine release seems to be related to the gastrin response and probably occurs at the level of enterochromaffin-like (ECL) cells; 3) the ethanol content of these drinks is not important for their stimulant effect, indicating that some other components of beer and wine are responsible for gastrin and histamine release from the dog stomach.

Gastric acid secretion after blockade of angiotensin AT 1 receptors in the Na +-depleted rat

This study tested the hypothesis that angiotensin II acting through the angiotensin AT 1 receptor plays an important role in the control of gastric acid secretion. Basal gastric acid secretion and gastric blood flow were lower in Na +-depleted animals, in which the renin-angiotensin system was activated, than in animals maintained on a normal Na + diet. Intravenous infusion of pentagastrin at 0.6 μg/kg/min increased gastric acid secretion to a greater extent in normal Na + than in Na +-depleted animals. In addition to stimulating gastric acid secretion, pentagastrin increased gastric blood flow by proportionally the same amount in both normal and low Na + animals. However, because basal gastric blood flow was considerably reduced in Na +-depleted animals, the increase produced by pentagastrin extended only to the levels observed in non-pentagastrin-treated normal Na + animals. Lower gastric blood flow in response to pentagastrin may explain the smaller increase in gastric acid secretion observed in Na +-depleted animals. In Na +-depleted animals, the selective angiotensin AT 1 receptor antagonist losartan did not affect basal gastric acid secretion or gastric blood flow, suggesting the involvement of mechanisms other than angiotensin II. Following blockade of angiotensin AT 1 receptors, pentagastrin significantly increased gastric blood flow in Na +-depleted animals to levels observed with infusion of the pentapeptide in normal Na + animals. The results suggest that the decrease in pentagastrin-stimulated acid secretion in Na +-depleted animals is mediated by angiotensin II acting through the angiotensin AT 1 receptor, most probably through vascular mechanisms.

Activation of somatostatin receptor subtype 2 inhibits acid secretion in rats.

Somatostatin is a potent inhibitor of gastric acid secretion. Recently, at least five distinct somatostatin receptor subtypes (SSTR) have been characterized and evaluated using relatively selective peptide analogues of somatostatin. We sought to determine which somatostatin receptor subtypes are involved in peripheral regulation of gastric acid secretion. Fasted, male Sprague-Dawley rats were anesthetized and were implanted with a double-lumen cannula in the stomach. Acid secretion was measured in gastric samples collected every 10 min by backtitration to pH 7. After a 30-min basal period, a 2-h intravenous infusion of pentagastrin (24 micrograms.kg-1.h-1 i.v.) was started. During the second pentagastrin hour, a 1-h intravenous infusion of either vehicle (0.1% canine serum albumin in 0.9% saline) or somatostatin receptor agonists was begun. The somatostatin receptor agonists included peptides with relative specificity for SSTR1-5 (somatostatin-14; 10 nmol.kg-1.h-1); SSTR2, SSTR3, and SSTR5 [SMS-(201-995); 10 nmol.kg-1.h-1]; SSTR2 (1-1,000 nmol.kg-1.h-1); SSTR3 (10-1,000 nmol.kg-1.h-1); and SSTR5 (10-1,000 nmol.kg-1.h-1). The SSTR2 agonist decreased pentagastrin-stimulated acid secretion dose dependently, from 82 +/- 7% of maximum acid output at 1 nmol.kg-1.h-1 to 4 +/- 7% of maximum at 100 nmol.kg-1.h-1. At 10 nmol.kg-1.h-1, the SSTR2 agonist inhibited acid secretion (40 +/- 7% of maximum) similarly to somatostatin (37 +/- 4% of maximum) and SMS-(201-995) (31 +/- 4% of maximum). The SSTR2 agonist inhibited acid secretion approximately 10- to 100-fold more potently than either the SSTR3 or the SSTR5 agonist. These results indicate that somatostatin regulates gastric acid secretion by activation of SSTR2 receptors.

Pentagastrin enhances gastric mucosal defenses in vivo: luminal acid-dependent and independent effects

Stimulation of acid secretion is associated with enhanced resistance of the gastric mucosa to damage by luminal acid. We studied the mechanism by which gastric mucosal defenses are modulated in a system in which mucus gel thickness, intracellular pH (pHi), gastric mucosal blood flow, and acid secretion can be measured simultaneously in vivo, using a recently developed microfluorometric technique. Intravenous infusion of pentagastrin in a dose associated with maximal acid secretion increased mucus gel thickness, pHi, and mucosal blood flow during superfusion with a neutral solution. Subsequent superfusion with an acidic buffer (pH 1.7) further increased blood flow to nearly three times basal. During superfusion with luminal acid, pHi fell more slowly and recovered toward baseline more quickly in pentagastrin-infused rats than in controls. Pretreatment with the H2-receptor antagonist cimetidine abolished the increased blood flow associated with pentagastrin, impairing pHi homeostasis, although cimetidine increased mucus gel thickness in the absence of pentagastrin. We conclude that gastric defense mechanisms at the preendothelial and postepithelial levels are enhanced during acid secretion as part of a histamine-dependent homeostatic mechanism that balances gastric protective mechanisms with acid secretion. The net result of these enhanced defenses is the preservation of gastric surface cell pHi despite the presence of a large proton gradient between lumen and blood.

Pentagastrin infusions in patients with panic disorder I. Symptoms and cardiovascular responses

Cholecystokinin (CCK) may mediate human anxiety and animal data suggest that cholecystokinin antagonists could provide an important advance in the treatment of anxiety disorders. The study of CCK receptor systems in psychiatric patients has, however, been severely limited by the lack of available probes. We utilized intravenous infusions of pentagastrin, a selective CCK-B receptor agonist, and studied behavioral and cardiovascular responses in 10 patients with panic disorder and 10 normal controls. Pentagastrin produced substantial symptomatology, including anxiety, and increases in heart rate and blood pressure, in both patients and controls. Patients were more sensitive to the panicogenic effects of the pentagastrin. Panic attacks occurred in 70% of patients and 0% of controls. Patients' symptom responses were very similar to their “typical” panic attacks and to symptoms produced by CCK 4. Pentagastrin provides a readily available alternative to CCK 4 for studying the CCK receptor system and exploring its involvement in human anxiety.

Pentagastrin infusions in patients with panic disorder II. Neuroendocrinology

Cholecystokinin (CCK) has well-documented anxiogenic effects in animals and normal people, and panicogenic effects in patients with panic disorder, but little is known about its neuroendocrine profile. We examined neuroendocrine responses to intravenous infusions of pentagastrin, a selective CCK-B receptor agonist, in 10 patients with panic disorder and 10 normal control subjects. Pentagastrin potently activated the hypothalamic-pituitary-adrenal (HPA) axis, but did not release growth hormone or any of several vasoactive peptides (neurokinin A, substance P, vasoactive intestinal peptide). The HPA axis response was unrelated to increases in symptoms. Panic patients did not differ from controls in neuroendocrine responses to the CCK agonist. Differential sensitivity to novelty stress accounted for the only patient-control differences in neuroendocrine profiles. The data suggest that CCK may help modulate normal HPA axis activity, but its anxiogenic effects are unrelated to its stimulatory effects on the HPA axis. Pentagastrin provides a safe and readily available probe for further study of CCK receptor systems in humans.

Nitric oxide mediates the inhibition by interleukin-1 beta of pentagastrin-stimulated rat gastric acid secretion.

Bolus injection of interleukin-1 beta (2 micrograms kg-1, i.v.) inhibited acid secretion induced by intravenous infusion of pentagastrin (8 micrograms kg-1 h-1) in the continuously perfused stomach of the anaesthetized rat. Administration of interleukin-1 beta did not modify mean systemic arterial blood pressure. Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, 2-10 mg kg-1, i.v.), but not dexamethasone (5 mg kg-1, s.c. twice over 16 h), restored the acid secretory responses to pentagastrin. The actions of L-NAME were reversed by the prior administration of L-arginine (100 mg kg-1, i.v.), but not by its enantiomer D-arginine (100 mg kg-1, i.v.). L-NAME (5 mg kg-1, i.v.) increased blood pressure but this was not the mechanism by which interleukin-induced acid inhibition was prevented, since similar systemic pressor responses induced by phenylephrine (10 micrograms kg-1 min-1, i.v.), had no such effect. These findings suggest that interleukin-induced inhibition of acid responses to pentagastrin involves synthesis of NO from L-arginine.

Role of gastric mucosal prostaglandin E2 in the inhibitory action of secretin and somatostatin on gastric acid secretion in the rat.

We investigated the effect of indomethacin on secretin- and somatostatin-induced inhibition of gastric acid secretion stimulated by intravenous infusion of pentagastrin (0.3 microgram/kg.h) in anesthetized rats. Intravenous administration of a prostaglandin synthesis inhibitor, indomethacin (2 mg/kg + 1 mg/kg.h), completely abolished the inhibition of gastric acid secretion induced by intravenous infusion of secretion (0.05 CU/kg.h). The inhibitory effect of intravenous infusion of somatostatin (Sandostatin; 0.2 micrograms/kg.h). The inhibitory the gastric acid was not significantly changed by indomethacin. Secretin significantly increased the gastric mucosal content of prostaglandin E2, and the increase was completely blocked by indomethacin. Somatostatin, however, had no significant effect on gastric mucosal prostaglandin E2. The results suggest that endogenous prostaglandin is involved in the mechanism of inhibition of gastric acid secretion by secretin, but not by somatostatin.

Role of endogenous secretin and cholecystokinin in intraduodenal oleic acid-induced inhibition of gastric acid secretion in rats

We investigated a possible role of endogenous secretin and cholecystokinin (CCK) in inhibition of gastric acid secretion induced by intraduodenal administration of oleic acid in rats. Intraduodenal administration of oleic acid emulsion in a dose of 1 mmol/hr resulted in significant inhibition of gastric acid secretion stimulated by intravenous infusion of pentagastrin (0.3 micrograms/kg/hr), and this was accompanied by an increase in the plasma concentration of both secretin and CCK, from 1.2 +/- 0.08 pM and 20.6 +/- 1.2 pM to 4.3 +/- 0.18 pM and 31.6 +/- 0.9 pM, respectively (P less than 0.001). Intravenous infusion of secretin (0.05 CU/kg/hr) inhibited pentagastrin-stimulated gastric acid secretion, but CCK-8 (0.03 micrograms/kg/hr) failed, although intravenous infusion of secretin and CCK in those doses produced plasma levels comparable to the levels achieved in response to oleic acid administration. Furthermore, the oleic acid-induced suppression of gastric acid secretion was blocked significantly by intravenous injection of rabbit anti-secretin serum (0.1 ml), but not by intravenous infusion of a CCK-receptor antagonist, CR 1409 (5 mg/kg/hr). Thus, the results of this study indicate that endogenous secretin rather than CCK is involved in the hormonal mechanism regulating the inhibition of gastric acid secretion by intestinal fat in rats.

Secretagogue-specific effects of interleukin-1 on gastric acid secretion

Interleukin-1 beta (IL-1 beta) has recently been shown to reduce the severity of experimental gastroduodenal damage and to inhibit acid secretion in the pylorus-ligated rat. In the present study, the effects of IL-1 beta on pentagastrin-stimulated acid secretion were compared with those of two other cytokines, namely IL-1 alpha and tumor necrosis factor (TNF) alpha. Also, the effects of IL-1 beta on gastric acid secretion stimulated by bethanechol or histamine were assessed. Anesthetized rats were pretreated intravenously with one of the cytokines, at doses in the 0.1-5 micrograms/kg range, 30 min before starting an intravenous infusion of pentagastrin. TNF alpha failed to significantly affect acid secretion, whereas IL-1 alpha and IL-1 beta exhibited significant inhibitory effects. For example, at a dose of 5 micrograms/kg, IL-1 alpha and IL-1 beta reduced acid secretion by 33 and 80%, respectively. The inhibitory effects of IL-1 beta on acid secretion could be completely inhibited by preincubation with an antibody directed against IL-1 beta but not by pretreatment with indomethacin (5 mg/kg sc) or by bilateral vagotomy. If acid secretion was stimulated by intravenous infusions of histamine or bethanechol, neither IL-1 beta nor TNF alpha produced significant inhibitory effects. Inhibition of acid secretion by IL-1 was also observed when the IL-1 was administered subsequent to stimulation by pentagastrin administration. These results demonstrate that IL-1 beta is an extremely potent inhibitor of acid secretion stimulated by pentagastrin but not that stimulated by histamine or bethanechol, through a mechanism that is at least in part independent of the vagus nerve and of prostaglandin synthesis. IL-1 alpha is less potent as an inhibitor of gastric acid secretion, whereas TNF appears to be inactive. Because pentagastrin-stimulated acid secretion could be completely inhibited by a histamine H2-receptor antagonist (cimetidine) and because IL-1 had no effect on histamine-stimulated acid secretion, it is possible that IL-1 exerts its antisecretory actions by inhibiting pentagastrin-stimulated histamine release.

Acid secretory changes and early relapse following duodenal ulcer healing with ranitidine or sucralfate

Controversial aspects relating to acid secretory changes following duodenal ulcer healing, and the effect of histamine-2 (H 2)-receptor blockers on such changes are discussed. Recent studies comparing the effects of ranitidine or sucralfate on changes in the acid secretory responses in the healing of duodenal ulcers are described, and the relevance of these changes to early relapse considered. The duration of therapy and timing of acid-secretory studies and endoscopies are standardized in all studies, but the acid-secretory parameters vary. These comprised acid secretory responses to graded doses of an intravenous infusion of pentagastrin or histamine, sham-feeding responses, and basal and nocturnal acid secretion. In all studies, healing with sucralfate was associated with a significant decrease in the various parameters of acid secretion. In the ranitidine-healed groups, no appreciable decrease was noted and there was, indeed, a significant increase in nocturnal acid secretion. Routine endoscopies performed 4–6 weeks after documented ulcer healing showed a recurrence of 3 of the 32 (9%) sucralfate-healed and in 14 of the 35 (40%) ranitidine-healed ulcers. Increased acid secretory responsiveness following duodenal ulcer healing was strongly correlated with subsequent early relapse.

Secretory Protein 7B2

Mean plasma concentrations of 7B2 in three patients with medullary carcinoma of the thyroid (MCT) (294 +/- 38 pg/ml) were significantly higher than those in age-matched normal subjects (107.2 +/- 7.2 pg/ml, n = 11). The intravenous infusions of pentagastrin (0.5 microgram/kg) markedly increased the plasma concentrations of 7B2 as well as calcitonin in all three MCT patients but it caused no significant rise of the plasma 7B2 concentration in any healthy subjects. The peak times and rates of increase of plasma 7B2 concentrations were different from those of plasma calcitonin concentrations in MCT patients. The plasma 7B2 concentration in one of the patients with MCT showed a marked reduction and no further elevation from the pentagastrin infusion following a total thyroidectomy (preop. 226 pg/ml; postop. 112.1 pg/ml). The above evidence suggests that the increased levels of plasma 7B2 in MCT patients may be attributed to the release from parafollicular cells of thyroid. Therefore, 7B2 is considered to be clinically useful as a tumor marker of MCT.