Autonomic nervous control of fundic secretion of somatostatin and antral secretion of gastrin and somatostatin in pigs

By selective catheterization of gastric veins, we studied the secretion of gastrin and somatostatin from the antrum and of somatostatin from the gastric fundus-corpus region in anaesthetized pigs with or without acute adrenalectomy. The secretion was studied during electrical stimulation of the vagus nerves and the splanchnic nerves and simultaneous irrigation of gastric lumen with fluids of high, low, and neutral pH. The corpus-fundus somatostatin response to vagal stimulation was biphasic with a short-lasting initial increase followed by a lasting inhibition, which was little influenced by intraluminal pH or adrenalectomy. In pigs with intact adrenals, antral somatostatin secretion was increased by vagal stimulation, whereas in adrenalectomized pigs, the effect was inhibitory. The vagally induced inhibition was abolished when the intragastric pH was kept at pH 2. The antral gastrin secretion was strongly stimulated by vagal stimulation. The magnitude of the secretory response was inversely related to the pre-stimulatory somatostatin levels, but not to the nerve stimulation responses. Splanchnic stimulation increased arterial blood pressure and gastric blood flow, but had inconsistent effects on somatostatin and gastrin secretion.     

The effect and mechanism of action of capsaicin on gastric acid output

Background  Capsaicin has beneficial pharmacological properties, such as the ability to improve appetite and digestion. However, capsaicin has been reported to suppress gastric acid output, but to increase secretion; no consensus as to its effects on gastric acid output has been reached, and the underlying mechanisms remain to be elucidated. Methods  Rat gastric lumen was perfused with capsaicin. Basal acid output and gastric acid secretion stimulated by vagal nerve activation and bethanecol, a muscarinic receptor agonist, were measured. After intravenous infusion of calcitonin gene-related peptide (CGRP), the measurements were repeated. The secretion of gastrin, somatostatin, and histamine was measured in isolated vascularly perfused rat stomach after vagal nerve and bethanecol stimulation, and under the influence of capsaicin. Results  Capsaicin administration had no effect on basal gastric acid output, but inhibited acid secretion resulting from vagal stimulation. Capsaicin had no effect on acid secretion resulting from stimulation with bethanecol. Administration of high-dose CGRP inhibited basal acid output and gastric acid secretion from both vagal nerve and bethanecol stimulation. Low-dose CGRP inhibited gastric acid secretion because of vagal stimulation, but had no effect on basal secretion or acid secretion following stimulation with bethanecol. Capsaicin administration inhibited the stimulated gastrin and histamine secretion and reversed the suppression of somatostatin secretion mediated by vagal stimulation. However, capsaicin had no effect on stimulated gastrin secretion, suppression of somatostatin secretion, or stimulated histamine secretion because of bethanecol. Conclusions  Capsaicin inhibited gastric acid output, and the mechanism underlying this effect appears to involve vagal nerve inactivation.     

Interactions between antral peptides and prostaglandin biosynthesis in gastric acid regulation in man

The role of endogenous prostaglandins as modulators of antral hormone release and gastric acid secretion was studied in the intact human stomach. The subjects (n = 9) received indomethacin prior to gastric perfusion at pH greater than 7 or less than 2 and subsequent vagal stimulation. Indomethacin was also tested against parenteral somatostatin (n = 10) and pentagastrin (n = 8). The release of somatostatin into the circulation was biphasic after vagal stimulation, and the plasma levels were inversely proportional to those of plasma gastrin. Acidification of the gastric antrum from pH greater than 7 to less than 2 increased twofold the basal plasma levels of somatostatin (p less than 0.05) and suppressed basal and vagally stimulated gastrin release (p less than 0.05) and gastric acid secretion (p less than 0.05). Indomethacin prior to acidification had little effect in the basal state. Following stimulation the release of somatostatin increased, as indicated by a twofold elevation of somatostatinlike immunoreactivity in the gastric lumen (p less than 0.05), but there was less inhibition of plasma gastrin (p less than 0.05) and gastric acid secretion (p less than 0.05) as compared to acidification alone. During alkaline gastric perfusion, indomethacin increased circulating somatostatin (p less than 0.05) levels without affecting plasma gastrin or gastric acid. Indomethacin given against intravenously infused somatostatin (0.1 microgram.kg-1.h-1) partially reversed the inhibited gastrin response to vagal stimulation without affecting somatostatin-suppressed gastric acid secretion. The effects of indomethacin against pentagastrin were marginal. In conclusion: Gastric acidification in man stimulates plasma release of somatostatin in parallel to suppressing gastrin release and gastric acid secretion. Endogenous prostanoids participate to regulate antral hormone interactions and may have dual actions on antral somatostatin, as negative modulators of release and as mediators of somatostatin effects on the gastrin cell. It is suggested that an unrestricted release of antral somatostatin is reflected in the gastric lumen rather than in the circulation.     

Control of acid secretion.

Receptors for the main neural (acetylcholine), hormonal (gastrin) and paracrine (histamine) secretory stimulants and the signal transduction pathways to which these receptors are coupled have been identified on the parietal cell. The stimulatory effect of histamine is mediated via an increase in adenylate cyclase activity, whereas the effect of acetylcholine and gastrin are mediated via an increase in cytosolic levels of calcium. Strong synergism between histamine and either gastrin or acetylcholine may reflect postreceptor interaction between the distinct pathways. Acetylcholine and gastrin are also capable of releasing histamine from the gastric mucosa, probably from ECL cells. The inhibitory effects of somatostatin and prostaglandin E on acid secretion are mediated by receptors coupled via guanine nucleotide binding proteins to inhibition of adenylate cyclase activity. All the pathways converge on and modulate the activity of the luminal enzyme, H+K(+)-ATPase, ultimately responsible for acid secretion. The intramural neural and paracrine pathways involved in the regulation of gastrin secretion in the antrum and acid secretion in the fundus have also been identified. Of prime importance is the somatostatin cell, which exerts a paracrine restraint on gastrin secretion and acid secretion. Elimination of this restraint or disinhibition is one of the mechanisms by which the stimulatory influence of cholinergic neurons is exerted on gastrin and parietal cells. Gastrin secretion is regulated by a cholinergic neuron that causes inhibition of somatostatin secretion and thus stimulation of gastrin secretion (disinhibition) and a noncholinergic neuron that causes direct stimulation of gastrin secretion by releasing the neurotransmitter, bombesin (or gastrin-releasing peptide). Acid secretion is regulated by a cholinergic neuron that causes direct stimulation of the parietal cell and indirect stimulation by decreasing somatostatin secretion, thus eliminating its inhibitory effect on the parietal cell (disinhibition). In addition, a regulatory feedback mechanism exists whereby intraluminal acidification stimulates somatostatin secretion, which in turn attenuates acid secretion. Gastric acid secretion may also be regulated by one or more intestinal inhibitory hormones, the most likely candidates being secretin, intestinal somatostatin, and neurotensin. Enterogastrone activity probably reflects the combined effect of all these hormones. Precise information on receptors and signal transduction mechanisms as well as on intramural neural and paracrine regulatory pathways has led to the development of new drugs capable of inhibiting acid secretion. These include antagonists that interact with stimulatory receptors (histamine H2-receptor antagonists, muscarinic receptor antagonists, and gastrin receptor antagonists), agonists that interact with inhibitory receptors (somatostatin and prostaglandin E analogues), and irreversible inhibitors of the luminal enzyme, H+K(+)-ATPase.     

Psychosensory initiation of gastric secretion in dogs. Inter-relation of vagal component, gastrin, histamine and somatostatin

The effects of vagal stimulation on gastric secretion and on blood gastrin, histamine and somatostatin release have been assessed in three esophagostomized dogs equipped with gastric fistula and Heidenhain pouch. The animals were submitted to sham feeding of variable duration (from 2.5 to 12.5 min) and composition. In response to standard composition of the sham feeding, acid and pepsin responses were observed in the gastric fistula only; they were closely related to the sham feeding duration. Integrated histamine responses were also closely related to sham feeding duration and were correlated with acid or pepsin responses. Gastrin was released by sham feeding induced-vagal stimulation, but there were no relationship between gastrin and secretory responses. Somatostatin release decreased as duration of sham feeding stimulation increased and correlated negatively with acid or pepsin responses. Modified standard sham feeding, by adding either lipids or glucids resulted in the same gastric and hormonal responses as standard sham feeding. It appears that 1 degree) vagal stimulation resulting in the psychosensorial receptors stimulation can be quantified, 2 degrees) histamine reduces somatostatin release and could represent a non cholinergic vagal mediator, capable of controlling somatostatin release in the cephalic phase of gastric secretion.     

Effects of H2-receptor antagonist on gastrin and somatostatin secretion of rat stomach

To investigate the effects of 14 days administration of H2-receptor antagonist (famotidine) on gastric gastrin and somatostatin secretion, bombesin and glucagon were perfused in the isolated pancreas-duodenum deprived rat stomach. Then serum gastrin concentration, gastric mucosal gastrin and somatostatin content, and gastric mucosal G-cell and D-cell numbers were examined. The 14 days administration of famotidine caused the significant increase of basal gastrin secretion, antral G-cell hyperplasia, high gastrin sensitivity to the stimulation by bombesin, and the low somatostatin sensitivity to the stimulation by glucagon. These facts would suggest that 14 days famotidine administration disturbed not only gastrin secretion but also somatostatin secretion. These results may contribute, at least in part, to the high recurrence of ulcers after withdrawal of H2-receptor antagonists.     

Central and peripheral vagal mechanisms involved in gastric protection against ethanol injury

Abstract Activation of medullary thyrotropin-releasing hormone (TRH), at a dose subthreshold to increase gastric acid secretion, protects the gastric mucosa against ethanol injury through vagal cholinergic pathways in urethane-anaesthetized rats. Peripheral mediators involve the efferent function of capsaicin-sensitive splanchnic afferents leading to calcitonin gene-related peptide (CGRP)- and nitric oxide (NO)-dependent gastric vasodilatory mechanisms. In addition, gastric prostaglandins participate in gastric protection through mechanisms independent of the stimulation of gastric mucosal blood flow and mucus secretion. Medullary TRH has physiological relevance in the vagal-dependent adaptive gastric protection induced by mild (acid or ethanol), followed by strong, irritants. Additional neuropeptides, namely peptide YY (PYY), somatostatin analogues, CGRP and adrenomedullin, also act in the brainstem to induce a vagal-dependent gastric protection against ethanol through interactions with their specific receptors in the medulla. Central PYY and adrenomedullin act through vagal cholinergic prostaglandins and NO pathways, while somatostatin analogue acts through vagal non-adrenergic, non-cholinergic vasoactive intestinal peptide and NO mechanisms. Although their biological relevance is still to be established, these peptides provide additional tools to investigate the multiple vagal-dependent mechanisms which increase the resistance of the gastric mucosa to injury.     

Effects of somatostatin-14 on gastric and pancreatic responses to hormonal and neural stimulation using an isolated perfused rat stomach and pancreas preparation

To study the role of somatostatin in the regulation of pancreatic and gastric functions, a combined isolated rat stomach and pancreas preparation was developed. This model allowed simultaneous measurements of exocrine and endocrine secretion from the pancreas and gastrin secretion from the stomach. Somatostatin was applied either by a linear gradient or by constant infusion with one concentration in the presence of cerulein, secretin, electric vagal activity, or acetylcholine. Somatostatin did not influence exocrine pancreatic secretion irrespective of what substance was stimulated. In contrast, somatostatin significantly inhibited glucose-dependent insulin and gastrin secretion, either basal or stimulated by vagal activity or acetylcholine. Acetylcholine-induced gastrin secretion was more sensitive to inhibition by somatostatin than insulin. We conclude that in an isolated perfused organ system somatostatin has potent inhibitory effects on endocrine pancreas and stomach but has no effect on exocrine pancreatic volume and enzyme secretion.     

Regulation of somatostatin secretion by gastrin- and acid-dependent mechanisms.

The regulation of gastric somatostatin is linked to changes in gastric acidity, with a number of studies showing a good correlation between somatostatin secretion and gastrin-stimulated luminal acidity. However, gastrin may also have direct effects on somatostatin secretion independent of the concurrent acid status. We have examined the relative contribution of gastrin itself vs. gastric acid on the increase in somatostatin secretion observed after gastrin administration. Pentagastrin administered to conscious sheep for 2 h caused a 10- to 12-fold increase in both portal venous and peripheral jugular venous plasma somatostatin levels. This was associated with a decrease in gastric pH from 3.5 to 1.7. When the sheep were pretreated with the proton pump inhibitor omeprazole to prevent any change in gastric acidity, pentagastrin caused a similar increase in plasma somatostatin. The increase in somatostatin could also be produced by gastrin-17 infusions. Thus, these studies demonstrate that in the conscious animal gastrin can stimulate somatostatin independent of changes in gastric acidity. It is proposed that there is a negative feedback between somatostatin and gastrin, which may modulate the acid secretory response to gastrin.     

Effect of glucagon-like peptide-1 on gastric somatostatin and gastrin secretion in the rat

The effect of glucagon-like peptide-1 (GLP-1) amide on gastric somatostatin and gastrin secretion was investigated in the isolated, vascularly perfused rat stomach preparation. GLP-1 (7-36) amide, 10(-12) to 10(-7)M, dose-dependently increased gastric somatostatin release, achieving maximal stimulation (314 +/- 15% above basal) at the highest dose. The somatostatin response to 10(-8)M GLP-1 (7-36) amide was not affected by concomitant perfusion with tetrodotoxin. GLP-1 (1-36) amide did not affect somatostatin release. Both basal and acetylcholine-stimulated gastrin were inhibited by GLP-1 (7-36) amide but were not influenced by GLP-1 (1-36) amide. In is concluded that GLP-1 (7-36) amide is the biologically effective peptide that stimulates gastric somatostatin and inhibits gastrin secretion, probably via non-neural pathways. GLP-1 (7-36) amide-induced inhibition of gastric acid secretion may, at least in part, be due to enhanced somatostatin and/or decreased gastrin release.     

Physiology and pathology of gastrin

Gastrin release does play a part in the cephalic phase of acid secretion in man and is the major mechanism for the gastric phase of acid secretion. The vagal control of gastrin release is most likely mediated by cholinergic and possibly non-cholinergic excitatory fibres, as well as by cholinergic inhibitory fibres. Gastric luminal control of gastrin release is by local food and possibly distension stimulation, as well as by acid inhibition. Of the various causes of hypergastrinaemia, those associated with gastrinoma, G-cell hyperfunction and retained antrum have definite pathogenetic roles. Duodenal ulcer disease is a heterogeneous goup of disorders having different pathogenetic mechanisms. Parietal cell hyperplasia and G-cell dysfunctions, consisting of modest to florid G-cell hyperfunction and hyperplasia with secondary parietal cell hyperplasia, are but some facets of abnormalities that we have been able to identify.     

Control of gastric acid secretion in somatostatin receptor 2 deficient mice: shift from endocrine/paracrine to neurocrine pathways

The gastrin-enterochromaffin-like (ECL) cell-parietal cell axis is known to play an important role in the regulation of gastric acid secretion. Somatostatin, acting on somatostatin receptor type 2 (SSTR(2)), interferes with this axis by suppressing the activity of the gastrin cells, ECL cells, and parietal cells. Surprisingly, however, freely fed SSTR(2) knockout mice seem to display normal circulating gastrin concentration and unchanged acid output. In the present study, we compared the control of acid secretion in these mutant mice with that in wild-type mice. In SSTR(2) knockout mice, the number of gastrin cells was unchanged; whereas the numbers of somatostatin cells were reduced in the antrum (-55%) and increased in the oxyntic mucosa (35%). The ECL cells displayed a reduced expression of histidine decarboxylase and vesicle monoamine transport type 2 (determined by immunohistochemistry), and an impaired transformation of the granules to secretory vesicles (determined by electron microscopic analysis), suggesting low activity of the ECL cells. These changes were accompanied by an increased expression of galanin receptor type 1 in the oxyntic mucosa. The parietal cells were found to respond to pentagastrin or to vagal stimulation (evoked by pylorus ligation) with increased acid production. In conclusion, the inhibitory galanin-galanin receptor type 1 pathway is up-regulated in the ECL cells, and the direct stimulatory action of gastrin and vagal excitation is enhanced on the parietal cells in SSTR(2) knockout mice. We suggest that there is a remodeling of the neuroendocrine mechanisms that regulate acid secretion in these mutant mice.     

Gastric acid secretion in uraemia and circulating levels of gastrin, somatostatin, and pancreatic polypeptide.

Basal circulating levels of gastrin, somatostatin, and pancreatic polypeptide were measured in 30 chronic haemodialysis patients. Five patients had considerably raised serum gastrin (greater than 400 pmol/1) and also gastric achlorhydria while 75% of the patients who had normal (less than 55 pmol/1) or moderately increased (less than 400 pmol/1) serum gastrin had raised maximal acid outputs. Patients with serum gastrin greater than 400 pmol/1 had significantly lower plasma concentrations of somatostatin compared with both healthy individuals and uaremic patients with normal gastrin levels. Raised serum concentrations of pancreatic polypeptide were observed in the majority of the patients but no correlation was found between this peptide and gastric acid secretion or circulating levels of gastrin and somatostatin, respectively. Prolonged circulation time for gastrin and pancreatic polypeptide was demonstrated after food stimulation. Prolonged gastrin stimulation of the parietal cell mass may lead to work hypertrophy and gastric acid hypersecretion. Whether long-standing over-stimulation by gastrin also may induce atrophy of the cells remains to be studied.     

Identification of the neurotransmitter/neuromodulator functions of the neuropeptide gastrin-releasing peptide in the porcine antrum, using the antagonist (Leu13-psi-CH2 NH-Leu14)-bombesin

We studied the effects of a new bombesin/gastrin-releasing peptide (GRP) receptor antagonist, Leu13-psi-(CH2NH)-Leu14-bombesin, on the secretion of gastrin and somatostatin and on the motor activity of isolated perfused porcine antrum in response to infusions of GRP at 10(-10) or 10(-9) mol/l and in response to electric stimulation of the vagus nerves. GRP significantly increased the secretion of gastrin and somatostatin and increased the frequency of antral contractions threefold. At 0.5 x 10(-6) mol/l the antagonist completely abolished the effects on motality and gastrin secretion and strongly inhibited the effect on somatostatin secretion. Vagus stimulation significantly increased gastrin and somatostatin secretion and increased the contraction frequency threefold. The antagonist strongly inhibited the somatostatin response, abolished the motility effects and reversed the stimulatory effect on gastrin secretion to a significant inhibition. Assuming that the antagonist interacts specifically with GRP receptors, we conclude that our data strongly support the concept that GRP-producing nerves are essential for vagally induced secretion of gastrin and somatostatin from the antrum. The GRP nerves may also play a role in the control of gastric motor activity.     

Selective ligand-induced intracellular calcium changes in a population of rat isolated gastric endocrine cells

BACKGROUND & AIMS: Peripheral regulation of acid secretion depends mainly on stimulation or inhibition of the three major gastric endocrine cells (enterochromaffin-like, gastrin, and somatostatin). The aim of this paper was to define physiological responses of enterochromaffin-like, gastrin, and somatostatin cells in a mixed endocrine cell population by measuring ligand-selective changes of intracellular calcium ([Ca2+]i) in individual cells. METHODS: Endocrine cells were enriched from a rat gastric cell suspension by elutriation, a density-gradient fractionation, and a 48-hour short-term culture. [Ca2+]i responses of individual cells to various ligands such as gastrin/carboxy-terminal cholecystokinin octapeptide and selective cholecystokinin antagonists, carbachol, and gastrin-releasing peptide were monitored using video imaging in a perfusion chamber. Characteristic [Ca2+]i changes distinguished the three cell types, confirmed by immunostaining. RESULTS: All enterochromaffin-like cells respond to cholecystokinin-B receptor stimulation, but only a few respond to carbachol. Gastrin cells respond to both gastrin-releasing peptide and carbachol but not to cholecystokinin-receptor agonists. Somatostatin cells have both stimulatory cholecystokinin-A and cholecystokinin-B receptors and inhibitory muscarinic receptors. All cells have inhibitory somatostatin receptors. CONCLUSIONS: Calcium- signaling responses of gastric endocrine cells are distinctive. This allows individual cell types in a mixed population to be characterized and permits an analysis of the hormones and transmitters that act directly on a specific cell type. (Gastroenterology 1996 Jun;110(6):1835-46)     

Effect of systemic gastric acid stimulation and intragastric pH changes on synchronous antral gastrin and somatostatin release in anesthetized,nonatropinized duodenal ulcer patients and controls

The synchronous changes in antral gastrin and somatostatin release in anesthetized, nonatropinized duodenal ulcer patients and control subjects were investigated by serial intraoperative blood sampling from the right gastroepiploic vein. The mean basal antral plasma gastrin and somatostatin concentrations of the two groups did not differ significantly. The significantly greater gastric acid secretory response to systemic gastric acid stimulation (pentagastrin stimulation) in duodenal ulcer patients compared with that of control subjects was not linked to any difference in antral somatostatin release pattern. The decrease in antral plasma gastrin release was significantly lower after acid instillation and the increase was significantly higher after alkali instillation in duodenal ulcer patients compared with those of controls, indicating an abnormal gastrin response to intragastric pH changes in duodenal ulcer patients, which was again not found to be coupled to any significant difference in antral somatostatin release. The results suggest that an abnormal somatostatin-mediated inhibition of gastrin release and/or gastric acid secretion does not exist in duodenal ulcer patients.     

Abdominal pathways and central origin of rat vagal fibers that stimulate gastric acid

The brainstem location and peripheral course of the vagal preganglionic fibers that stimulate gastric acid secretion were identified using electrical stimulation combined with retrograde (True Blue; Dr. K. G. Illing, Gross Umstadt, Germany) and anterograde (Dil; Molecular Probes) fluorescent neural tracers in rats with various selective vagotomies. Animals with only one or both gastric branch(es) spared had normal, large gastric acid responses to electrical stimulation of the ipsilateral cervical vagus and showed an abundance of Dil-labeled vagal fibers and terminals in the gastric myenteric plexus. Rats with only the unpaired hepatic branch spared had a much smaller but significant gastric acid response and a few labeled vagal profiles in the antral region of the stomach. In contrast, rats with only one or both celiac branch(es) intact had neither a gastric acid response, nor evidence for Dil transport to the stomach. Retrograde transport of True Blue through the spared vagal axons to the brainstem indicated that the cell bodies of the preganglionics that send their axons through the acid-positive gastric and hepatic branches occupy the medial longitudinal columnar subnuclei of the dorsal motor nucleus. It is concluded that besides the long-recognized gastric branches, which are the major access route to the parietal cells, the hepatic branch contains a small number of fibers that most likely reach the antrum through the right gastroepiploic artery along the greater curvature and/or the right gastric artery.     

Influence of chronic drug-induced achlorhydria by substituted benzimidazoles on the endocrine stomach in rats

The release of gastric somatostatinlike immunoreactivity and gastrin was studied in rats with chronic achlorhydria induced by the substituted benzimidazole BY 308. In vitro, stimulation of gastrin release by acetylcholine was slightly enhanced after 1 day of treatment but no further effects were observed compared to placebo controls. Four weeks of treatment evoked marked gastrin hypersecretion, which was atropine-resistant. Stimulation of gastrin release was inversely correlated to enhancement of basal gastrin levels. Chronic achlorhydria distinctly reduced somatostatin responses to isoproterenol, whereas potent stimulation was observed in controls. Treatment with BY 308 for 1 wk was associated with fully developed gastrin hypersecretion but isoproterenol-stimulated somatostatin release was still unaffected. Hypergastrinemia accompanied by increased antral gastrin and reduced antral and fundic somatostatin concentrations was also found in vivo after 4 wk of treatment with BY 308. It is concluded that chronic achlorhydria not only enhances storage and secretion of gastrin but also diminishes the secretion and tissue stores of somatostatin; adaptive changes of the somatostatin cell occur, however, with a much longer delay.     

Effects of [Asu1,7]-eel calcitonin on gastric somatostatin and gastrin release.

Effects of [Asu1,7]-eel calcitonin on gastric somatostatin and gastrin secretion were studied by using the isolated perfused rat stomach. [Asu1,7]-eel calcitonin (10(-9)--10(-7)M) caused a simultaneous dose-dependent increase of gastric somatostatin release and decrease of gastrin secretion, with a significant correlation between these two. The demonstration of calcitonin stimulation of gastric somatostatin release raises the possibility of somatostatin-mediated suppression of gastrin secretion by calcitonin.     

Role of vagus nerve for release of gut hormones

The role of vagus nerve for release of gastrin, secretin and somatostatin in dogs was studied. Bilateral cervical vagotomy and electric vagal stimulation (25 V 0.5 msec 10 Hz) were performed and blood levels of gut hormones were measured. After vagotomy, blood levels of gastrin, secretin and somatostatin did not change. The electric vagal stimulation elevated blood level of gastrin. Atropine and hexamethonium inhibited the elevation. The electric vagal stimulation did not change blood levels of secretin and somatostatin. In conclusion, vagal stimulation releases gastrin into blood circulation depending on the cholinergic mechanism.