Gastrin in duodenal and jejunal tissue and in plasma following antrectomy with gastrojejunostomy

The gastrin concentration in the proximal third of the duodenum was found to be increased in dogs following antrectomy with gastrojejunostomy. The level found 13–15 weeks after operation was, using a COOH-terminal directed antiserum, 27.8±4.5 pmol/g tissue wet weight (mean value ± SE, n=5), which is approximately 4 times higher than the concentration found in the same tissue of unoperated dogs. In the middle and distal thirds of the duodenum the gastrin concentrations were 6.1±0.6 and 5.2±0.2 pmol/g (n=5), respectively. These values are not significantly different from those of the corresponding tissues of unoperated dogs. The gastrin concentration was also determined in different parts of the jejunum. In specimens taken close to the gastrojejunostomy, the gastrin level was 1.9±0.2 pmol/g,-which was not significantly different from that in more proximal (3.0±0.3) or distal (1.7±0.2) parts of the jejunum in the same animals. Basal plasma gastrin concentration as measured with the same COOH-terminal directed antiserum, was reduced after surgery to 35% (mean value) of the preoperative level and remained low throughout the postoperative period. In contrast to this, using an antiserum directed against the NH₂-terminal portion of gastrin-17, the plasma gastrin concentration was found to be decreased to 70% 1–2 days after antrectomy and then to increase again and remain at approximately the preoperative level. The plasma gastrin concentrations measured with this antiserum, were consistently much higher than those measured with the COOH-terminal directed antiserum. In a previous study we have shown that the gastrin concentration in the proximal third of the canine duodenum is increased 20-fold at 14–16 weeks after antrectomy with gastroduodenostomy. In the present study it is shown that there is a less prominent increase after antrectomy with gastrojejunostomy. These results indicate that the presence of food and gastric juice in the duodenum might be of importance for the increase in duodenal gastrin after antrectomy.     

The effect of antrectomy on the number of gastrinimmunoreactive cells in the canine duodenum

The number of gastrin-immunoreactive cells in the duodenum was assessed by immunohis-tochemistry in 10 dogs that had been subjected to antrectomy with gastroduodenostomy (Billroth I), in 4 dogs in which an antrectomy with gastrojejunostomy (Billroth II) had been performed and in 4 unoperated controls. Gastrin-immunoreactive cells were found only in dogs that had been subjected to antrectomy ad modum Billroth I and then only within the first 30 mm of the duodenum, i. e. in the duodenal bulb. The gastrin cells occurred scattered on the villi, in the crypts and within the glands of Brunner. In 3 of the dogs patches of antral-type mucosa occurred within the first 10 mm of the duodenum. All dogs in which gastrin-immunoreactive cells were found have in a previous study been shown to have a markedly increased tissue concentration of gastrin in the proximal third of the duodenum compared to unoperated controls. In the dogs subjected to antrectomy ad modum Billroth II in which no cells were observed the level of gastrin in duodenal tissue has been found to be moderately elevated compared to that of control dogs. The results indicate that the increased gastrin concentration in the proximal third of the duodenum following antrectomy ad modum Billroth I corresponds to an increase in the number of gastrin-immunoreactive cells in the duodenal bulb.     

The effect of lowering the 5-hydroxytryptamine content of the rat spinal cord on analgesia produced by morphine

After prolonged fasting the activity of histidine decarboxylase in the oxyntic mucosa of the rat stomach is low. Feeding or injection of gastrin or insulin rapidly raises the enzyme activity. It was earlier suggested that all enzyme-activating agents act through release of gastrin. This view has found experimental support in studies which show that in antrectomized rats the enzyme is activated by gastrin but not by gastrin-releasing stimuli like feeding or vagal excitation (insulin hypoglycemia). In the present investigation rats were subjected to a variety of treatments and serum gastrin concentrations and gastric histidine decarboxylase activities were measured. The main findings were as follows.1. Feeding raised the serum gastrin level and the enzyme activity in unoperated rats. In fasted antrectomized rats the serum gastrin concentration was low; in freely fed antrectomized rats it was at the same level as in fasted unoperated rats. In antrectomized rats the enzyme activity was low and not raised by feeding.2. Acid in the antrum inhibits the release of gastrin whereas an alkaline pH may facilitate such release. All treatments that blocked acid secretion, thereby raising the antral pH, also raised the serum gastrin concentration and concomitantly the histidine decarboxylase activity. Thus, vagotomy increased the serum gastrin level and the histidine decarboxylase activity in fasted rats. Treatment of fasted unoperated rats with atropine or hexamethonium had similar effects. Antral exclusion, which prevents HCl from reaching the pyloric glands, resulted in marked increase in the serum gastrin concentration and in the enzyme activity of fasted rats.3. Injection of insulin resulted in a rather slow, progressive increase in the serum gastrin concentration. The peak was reached after about 4 hr. The enzyme activity was also raised markedly and the peak response occurred about 1 hr later.4. An increase in the histidine decarboxylase activity was invariably preceded or accompanied by a raised serum gastrin level. With fasted or fed unoperated, vagotomized, antrectomized or antrally excluded rats, the correlation coefficient for the relation between enzyme activity and serum gastrin concentration was 0.69 (P < 0.05).5. Porta-caval-shunted fasted rats responded to feeding or injection of insulin with marked activation of gastric histidine decarboxylase. The response after feeding was at least 5 times higher in shunted than in nonshunted rats but serum gastrin was only slightly higher. Following antrectomy of porta-caval-shunted rats feeding no longer raised the enzyme activity. Thus, the enzyme-activating agent was of antral origin. In the shunted rats injection of pentagastrin induced an enzyme activation about 5 times that seen in intact rats. This response was not significantly reduced by antrectomy.In conclusion, we have observed a correlation between serum gastrin concentration and histidine decarboxylase activity. We have failed to obtain evidence for the existence of any physiological intermediate other than gastrin in the activation of histidine decarboxylase induced by feeding, vagal stimulation or inhibition of acid secretion.     

Antrum participates in the postprandial augmentation of the acid response to exogenous gastrin in conscious cats

A humoral mechanism, potentiating the maximal acid, but not the pepsin response to exogenous gastrin in cats, is activated by protein-rich food in the stomach or duodenum, but not in the jejunum. In the present study, the effect of an oral meat meal on the maximal acid response to pentagastrin was investigated in Heidenhain pouch (HP) cats, and in antrectomized HP cats with duodenal exclusion and gastrojejunostomy Rouxen-Y. Antrectomy and duodenal exclusion abolished the postprandial HP acid response, and feeding did not potentiate the acid response to pentagastrin. The finding suggests that the gastrin-potentiating mechanism in the stomach is localized in the antrum, and it cannot be demonstrated in the jejunum. The basal plasma levels of gastrin and somatostatin did not differ in antrectomized and non-antrectomized cats. Antrectomy and duodenal exclusion abolished the postprandial gastrin and somatostatin responses. The plasma somatostatin increase during pentagastrin infusion persisted after antrectomy and duodenal exclusion. It is concluded that the antrum is not mandatory for the basal plasma levels of gastrin and somatostatin, but the postprandial gastrin response is of antral origin and may release somatostatin. Pentagastrin infusion releases extra-antral somatostatin in cats.     

Differential effect of bombesin on intraluminal and intravascular release of gastric gastrin and somatostatin in anaesthetized rats

The aim of the present investigation was to study how bombesin, gastrin-17, cholecystokinin-8 (CCK-8) and electrical vagal stimulation influence the release of gastrin and somatostatin into the gastric lumen. Bombesin (3 and 30 nmol kg-1 h-1), gastrin-17 and CCK-8 (10 nmol kg-1h-1) were infused i.v. and vagal stimulations at 5 V, 2 ms, 5 Hz were performed in anaesthetized rats, in which the stomach was perfused with a dextran solution (pH approximately 6 or approximately 1.5). pH, gastrin and somatostatin levels were measured in the perfusate after having passed the stomach. In addition, blood samples were drawn from the jugular vein in the experiments in which bombesin was infused. Gastrin and somatostatin levels were determined with radioimmunoassay, and gastrin- and somatostatin-like immunoreactivity will be referred to as gastrin and somatostatin below. Infusion of bombesin, 3 and 30 nmol kg-1 h-1, did not influence acid secretion as evidenced by an unchanged intraluminal pH. Nor was the intraluminal secretion of gastrin or somatostatin influenced by bombesin, whereas plasma gastrin and somatostatin levels were significantly increased at the higher dose. In contrast, infusion of CCK-8 and gastrin-17 (10 nmol kg-1 h-1), as well as electrical vagal stimulation, significantly decreased the pH and increased the somatostatin levels in the perfusate. Vagal activation in addition increased the gastrin levels. The present results, demonstrating that bombesin influences plasma and perfusate levels of gastrin and somatostatin differently, indicate that intraluminal and intravascular gastrin and somatostatin release may be separately regulated.     

Molecular Forms of Gastrin in Antral Mucosa,Plasma and Gastric Juice during Vagal Stimulation of Anesthetized Cats

Gastrin was released by electrical vagal stimulation in anesthetized cats. Antral mucosa, blood and gastric juice samples collected during vagal stimulation were subjected to gel filtration in order to characterize the different molecular forms of gastrin. In antral mucosa component III (gastrin-17) predominated. Besides, the antrum contained 5 per cent component II (gastrin-34, “big” gasirin), I per cent component I and trace amounts of component IV (gastrin-14 or “mini” gastrin). Immediately after vagal stimulation, component III (gastrin-17) appeared in the gastric venous effluent followed within a few minutes by component IV (gastrin-14). Component I and II (gastrin-34) were not detectable in any of the plasma samples. We suggest that component III (gastrin-17) is released from the antral mucosa and is then rapidly metabolized to component IV (gastrin-14) possibly to a significant extent in the fundic region of the stomach. Large amounts of component III (gastrin-17) were found in the vagally-induced gastric juice. Only very small amounts of degradation products were present, indicating that cat gastrin is relatively resistant to peptic degradation and acid hydrolysis.     

Light and Electron Microscope Localization of G-17-and G-34-like Immunoreactivities of Human Gastrinomas

Gastrin-17 (G-17) and gastrin-34-like immunoreactivities of human gastrinoma cells were investigated at light and electron microscope level using N-terminally directed antisera. The procedure includes (a) the 24 hr/immunoperoxidase staining of Bouin-fixed paraffin embedded tissues, (b) the immunoelectron microscopic labelling of aldehydefixed Epon-embedded tissues according to the immunogold technique. On light microscopy, a variable number of tumor cells stained for G-34. In contrast, G-17 immunoreactivity was very low or undetectable in the tumor material, although it was easily detected in endocrine cells of similarly processed human pyloric mucosa. On electron microscopy, most of the tumor cell granules belonging to the round compact or dense-cored type exhibited a variable labelling for G-34, whereas the vacuolar/floccular type remained unlabelled. In contrast, the labelling for G-17 occurred over most of the tumor cell granules, whether compact or floccular. Dense granules of varying size and shape, previously shown to store C-terminal gastrin immunoreactivity, were only faintly labelled by the two antisera. When compared to the labelling pattern of human pyloric G-cells, the predominance of round dense granules with G-34 and G-17 immunoreactivity in gastrinoma cells suggests an incomplete or defective post-translational processing of the precursor peptide.     

The occurrence of Gastrin-17 in the heart

Radioimmunoassay revealed gastrin-like immunoreactivity in extracts of the heart muscle from cat, guinea pig, rabbit and hog. The immunoreactivity was unevenly distributed, the highest levels being observed in extracts from the atria of the cat heart: in the right atrium ?1000 pg/g or 450 pmol/kg and in the left atrium ?4400 pg/g or 2000 pmol/kg. In extracts from the cat atria the gastrin-like immunoreactivity was identified as Gastrin-17. The preponderant localization of gastrin to the atria is suggested to be due to the distribution of gastrin containing vagal fibres and nerve terminals in that area, even if a possible localization to specific receptors, Purkinje fibres etc. cannot be excluded. A modulating action on the vagal influence on the heart, either on neurotransmission or on the receptor level, or a direct (perhaps trophic) effect on biochemical processes in the muscle are suggested as possible biological functions of the heart gastrin.     

Inhibition of gastric acid secretion inthe Atlantic cod, Gadus morhua, by sulphated and desulphated gastrin, caerulein, and CCK-octapeptide

Gastric acid secretory effects of gastrin/CCK-like peptides have been assayed in cods rendered "spontaneously" secreting by a continuous intestinal perfusion with diluted (33%) seawater. A high dose of pentagastrin induced a weak stimulation (31%) of acid output, while gastrin 17-II, caerulein and CCK8 were inhibitory. Caerulein was the most potent peptide, with an estimated D50 for inhibition of 0.013 nmol/kg.h. Although displaying lower potencies, also the desulphated forms of gastrin-17, caerulein and CCK8 were inhibitory. The results may be explained by release of an endogenous inhibitor, or by interaction with endogenous "codfish gastrin". In the latter case two alternatives are considered: Either gastrin 17, CCK8, and caerulein possess lower efficacies than "codfish gastrin" and therefore act as partial agonists. Alternatively, "codfish gastrin" is itself an inhibitory principle (gastron), the effect of which is mimicked by gastrin 17, caerulein and CCK8. The actions of gastrin and the gastrin-like peptides in the cod indicate a structure-activity relationship different from previously described systems, both mammalian and submammalian.     

Increase in duodenal tissue gastrin in dogs following antrectomy with gastroduodenostomy and after total gastrectomy with oesophagoduodenostomy1

The gastrin concentration in plasma and duodenal tissue was determined in dogs following antrectomy and total gastrectomy as well as in unoperated control animals. The first week after both types of operations, during which time the dogs were parenterally fed the basal plasma gastrin concentration was markedly reduced, and then it slightly increased. The increase in plasma gastrin concentration from the second postoperative week until sacrifice was found to be statistically significant in one of six antrectomized dogs and in two of three dogs in which the whole stomach had been resected. In unoperated controls the gastrin concentration in the proximal third of the duodenum was found to be 6.8±0.8 pmol/g tissue wet weight (mean value ± SE, n=11). Following antrectomy a time dependent increase was seen, the corresponding values being 11.0±2.5 (n=4), 36.4±15.7 (n=6) and 136.1±44.2 (n=6) pmol/g at 3, 9–10 and 14–16 weeks after operation, respectively. A similar increase was seen following total gastrectomy. 8 weeks after this type of operation the concentration was 22.2±12.5 (n=3) pmol/g. The gastrin concentration of the middle and distal thirds of the duodenum was not changed by the operations. The results show that removal of the main source of gastrin, i. e. the pyloric antrum, induces an increase in the tissue level of gastrin in the upper portion of the duodenum.     

Inhibition of gastric acid secretion in the Atlantic cod,Gadus morhua,by sulphated and desulphated gastrin,caerulein, and CCK-octapeptide

Gastric acid secretory effects of gastrin/CCK-like peptides have been assayed in cods rendered “spontaneously” secreting by a continuous intestinal perfusion with diluted (33%) seawater. A high dose of pentagastrin induced a weak stimulation (31 %) of acid output, while gastrin 17–11, caerulein and CCK8 were inhibitory. Caerulein was the most potent peptide, with an estimated D₅₀for inhibition of 0.013 nmol/kg h. Although displaying lower potencies, also the desulphated forms of gastrin-17, caerulein and CCK8 were inhibitory. The results may be explained by release of an endogenous inhibitor, or by interaction with endogenous “codfish gastrin”. In the latter case two alternatives are considered: Either gastrin 17. CCK8, and caerulein possess lower efficacies than “codfish gastrin” and therefore act as partial agonists. Alternatively, “codfish gastrin” is itself an inhibitory principle (gastrin). the effect of which is mimicked by gastrin 17. caerulein and CCK8. The actions of gastrin and the gastrin-like peptides in the cod indicate a structure-activity relationship different from previously described systems, bot mammalian and submam-malian.     

The role of the antrum and the vagus nerve in the formation of gastric mucosal histamine

1. The effects of the vagus nerve and of antral gastrin on the rate of histamine formation (histamine forming capacity, HFC, i.e. histidine decarboxylase activity) in the parietal cell region of the gastric mucosa has been investigated in the following stomach preparations: gastric fistula, denervated Heidenhain pouch, antral resection with gastrojejunostomy, gastrojejunostomy with exclusion of the duodenum and in the intact stomach. The determinations of mucosal HFC were made on fasting rats and on re-fed animals when the effect of feeding was studied.2. In fasting rats with a gastrojejunostomy and the antrum intact the mucosal HFC of the innervated stomach was about 4 times higher than in the corresponding preparation with the antrum resected. In the innervated main stomach the mucosal HFC was about twice as high as in the denervated pouch, indicating that the vagus and endogenous antral gastrin each contribute to maintaining mucosal HFC in the fasting state.3. Acidifying the stomach caused a substantial lowering of the mucosal HFC presumably by inhibiting antral gastrin release, whereas acid in the stomach did not interfere with the elevation of mucosal HFC evoked by injection of gastrin.4. Injection of gastrin elevated mucosal HFC in the innervated main stomach and in the denervated pouch to approximately equal levels. With the dose of gastrin employed there was about a fourfold increase in the HFC of the pouch mucosa.5. In antrectomized rats enhanced vagal influence, evoked by insulin injection or by feeding, raised the mucosal HFC. In rats with the antrum intact and the stomach acidified, insulin injection produced an increased HFC. Thus, a vagal effect on mucosal HFC exists independent of participation of antral gastrin.6. The stable choline esters carbachol and methacholine act directly on the parietal cell without involving mucosal HFC. The vagus nerve and gastrin, however, are assumed to provide secretory stimulation by means of accelerated histamine formation.7. The interrelation between increased histamine formation and hydrochloric acid secretion is discussed.     

Regulatory peptides in Barrett's oesophagus

Barrett's epithelium refers to the presence of ectopic mucosal types in the squamous-lined oesophagus. Previous studies have documented argentaffin and argyrophil-positive cells as well as gastrin-like immunoreactivity in oesophageal tissue extracts from patients with Barrett's mucosa. In the present study, 125 oesophageal biopsies obtained under direct vision at endoscopy from 22 patients with Barrett's oesophagus were systematically studied using fluorescence and peroxidase antiperoxidase single and double-staining immunocytochemical methods employing highly specific antibodies to localize the following peptide-containing cell types in Barrett's mucosa: gastrin, somatostatin, gastric inhibitory polypeptide, motilin, neurotensin and pancreatic glucagon. In addition, EC cells were localized using a cytochemical silver staining method. The results of this study indicate that EC cells and gastrin- and somatostatin-containing endocrine cells are detectable in Barrett's epithelium.     

Modification of the Gastric Secretory Response to Sham Feeding by Acidification of the Antrum and the Duodenum in Dogs

The effect of closure of a gastric cannula on the acid response to sham feeding was studied in Pavlov-pouch dogs with intact antro-duodenal regions as well as in antrectomized dogs with gastroduodenostomies. In the latter dogs, the sham feeding response was augmented by infusions of low doses of exogenous gastrin. The acid output after sham feeding in intact dogs was reduced on average by 59% by closure of the gastric cannula. In antrectomized dogs receiving a back-ground stimulation with gastrin, the response to ham feeding was not inhibited by closure of the cannula. The results suggest that the observed hypersecretory response to sham feeding after diversion of gastric acid from antrum and duodenum is mainly due to inactivation of antral inhibitory mechanisms. The pepsin secretion following sham feeding was not consistently changed by closure of the gastric cannula.     

Immunostaining of antral gastrin cells is quantitatively increased in Helicobacter pylori gastritis

The amount of gastrin-like immunostaining in gastrin (G) cells of the antral mucosa was quantified using a computer-assisted method of measuring immunoreaction product. Biopsies from 25 patients without Heliobacter-like organisms and 60 patients with varying degrees of infection were immunostained for gastrin. Twenty-five G cells from each patient were measured both subjectively and by image analysis. Gastrin-like immunoreactivity was found to be significantly increased in the presence of Heliobacter-like organisms.     

Molecular forms of gastrin in antrum and duodenum after parietal cell vagotomy

We examined whether parietal cell vagotomy (PCV) changed the distribution between the different molecular forms of gastrin. Serum, antrum, and duodenum from PCV patients, unoperated duodenal ulcer (DU) patients and control subjects were studied. PCV was followed by a twofold increase in the serum gastrin concentration, while the distribution between small and large gastrins were unaffected. However, sulfation of antral gastrins was reduced from 45 percent in unoperated DU patients to 34 percent in PCV patients (p less than 0.01). We conclude that gastrin sulfation is diminished after PCV. Diminished sulfation seems to be correlated to hypergastrinaemia of antral origin and not to specific diseases.     

Modification of the gastric secretory response to sham feeding by acidification of the antrum and the duodenum in dogs.

The effect of closure of a gastric cannula on the acid response to sham feeding was studied in Pavlov-pouch dogs with intact antro-duodenal regions as well as in antrectomized dogs with gastroduodenostomies. In the latter dogs, the sham feeding response was augmented by infusions of low doses of exogenous gastrin. The acid output after sham feeding in intact dogs was reduced on average by 59% by closure of the gastric cannula. In antrectomized dogs receiving a back-ground stimulation with gastrin, the response to ham feeding was not inhibited by closure of the cannula. The results suggest that the observed hypersecretory response to sham feeding after diversion of gastric acid from antrum and duodenum is mainly due to inactivation of antral inhibitory mechanisms. The pepsin secretion following sham feeding was not consistently changed by closure of the gastric cannula.     

Localization and identification of neurons with cholecystokinin and gastrin-like immunoreactivity in wholemounts of Aplysia ganglia

Immunohistochemical procedures were applied to wholemounts of the central nervous system and posterior intestine of the mollusc, Aplysia californica, to facilitate localization of cells that were immunoreactive to several antisera recognizing various epitopes of the peptides cholecystokinin and gastrin. Only antisera that recognized the carboxyl terminal sequence common to cholecystokinin and gastrin reacted with the Aplysia tissues tested. Intracellular electrophysiological studies of identified postsynaptic targets of immunoreactive neurons in the cerebral ganglia indicated that mammalian forms of gastrin 1-17, several cholecystokinin fragments, and the related peptide, amphibian caerulein, did not mimick the synaptic response mediated by the immunoreactive presynaptic neurons. Combinations of electrophysiological, immunohistochemical, and biochemical studies of several neurons in the buccal ganglia indicated that neurons B7 and B13 were immunoreactive to antisera against cholecystokinin and gastrin and that neuron B13 also contained a concentration of the neurotransmitter acetylcholine as high as in the identified cholinergic buccal neurons, B4 and B5. Several differences in the immunoreactivity of the various antisera were observed. Only one of the antisera was effective in staining neurons in the abdominal ganglia and another antiserum stained subsets of neurons that were immunoreactive to most of the other antisera recognizing the carboxyl terminus common to cholecystokinin and gastrin. The giant serotoninergic metacerebral neurons in Aplysia were not immunoreactive to the cholecystokinin/gastrin antisera even though it has been reported that the homologous neurons in a pulmonate mollusc contain cholecystokinin-like immunoreactivity. These studies demonstrated that there are many neurons with cholecystokinin/gastrin-like immunoreactivity in the Aplysia central and peripheral nervous system and suggested that the peptide may differ from vertebrate forms of cholecystokinin and gastrin. The identification of immunoreactive neurons with known postsynaptic target neurons and buccal neurons with acetylcholine co-localized with a cholecystokinin/gastrin-like peptide will facilitate elucidation of the functions of peptides in the nervous system since the Aplysia preparation is well known to be amenable to multidisciplinary studies.     

Glycine-extended gastrin-17 stimulates acid secretion only via CCK-2 receptor-induced histamine release in the totally isolated vascularly perfused rat stomach

The effects of gastrin precursors have been discussed during recent years. However, the mechanism for their action, whether through a novel receptor on the parietal cell or a cholecystokinin-2 (CCK-2) receptor on the enterochromaffin like (ECL) cells, is still not settled. This study examines the effect of glycine-extended gastrin-17 (Gly-G-17), the main non-amidated gastrin precursor, on gastric acid secretion and histamine release in the totally isolated vascularly perfused rat stomach. Glycine-extended gastrin-17 at the concentrations from 0.52 to 520 nmol L(-1) was administered to the totally isolated vascularly perfused rat stomach. Glycine-extended gastrin-17 at 52 or 520 nmol L(-1), and gastrin-17 at 0.52 nmol L(-1)were co-administered to examine whether glycine-extended gastrin augmented maximal gastrin stimulated acid secretion and histamine release. Both Gly-G-17 at 52 nmol L(-1) and gastrin-17 (G-17) at 0.52 nmol L(-1) were administered together with the histamine-2 receptor antagonist ranitidine at 10 micromol L(-1). Gastric acid and venous histamine output were measured. Glycine-extended gastrin-17 at lower concentrations from 0.52 to 5.2 nmol L(-1) did not stimulate gastric acid output or histamine release, whereas higher concentrations from 52 to 520 nmol L(-1) elicited a concentration-dependent increase in acid secretion and histamine release. The outputs of acid and histamine at 520 nmol L(-1) Gly-G-17 were at the same level as those found for G-17 at its maximally effective concentration of 0.52 nmol L(-1). Glycine-extended gastrin-17 at maximally effective concentration of 520 nmol L(-1) did not augment maximal gastrin stimulated acid secretion or histamine release. Ranitidine inhibited G-17 and Gly-G-17 stimulated acid secretion to a similar degree. This study confirms that the stimulatory effect of Gly-G-17 on gastric acid secretion is via a CCK-2 receptor on the ECL cell.     

Potentiation of the Gastric Secretory Response to Sham Feeding in Dogs by Infusions of Gastrin and Pentagastrin1

The gastric acid secretory response to sham feeding in dogs provided with esophagostomies and Pavlov pouches was related to the length of the sham feeding period. In antrectomized dogs the response even to prolonged sham feeding (30 min) was small. When a small supra-threshold dose (0.30 μg/kg/h) of synthetic human gastrin I or pentagastrin was infused, these dogs responded markedly to a short period of sham feeding (1 min), When the sham feeding period was prolonged to 10 min subthreshold amounts of gastrin and pentagastrin (0.06 μg/kg/h or less) sufficed to enhance the sham feeding response. The enhancement fulfilled the criterion proposed by Gaddum for true potentiation. The pepsin output was also increased when the sham feeding period was prolonged. In the antrectomized dogs pepsin output after sham feeding was not significantly changed when the dose of gastrin infused was increased from 0.06 to 0.30 μg/kg/h or when the dose of pentagastrin was increased from 0.30 to 1.20 μg/kg/h.