Somatostatin and the interdigestive migrating motor complex in man

The relationship between somatostatin and the interdigestive migrating motility complex (MMC) was determined in human volunteers. Motor activity was monitored manometrically by means of seven perfused catheters: four in the stomach, one in the duodenum, two in the jejunum. Blood samples were drawn every 10 min and radioimmunoassayed for motilin, pancreatic polypeptide and somatostatin. In four volunteers two activity fronts (AF) were recorded and somatostatin levels correlated to the manometric data. The start of an AF in the upper duodenum was accompanied by somatostatin peaks. Peak values, taken as the mean of the levels in the sample obtained after the start of an AF, the preceding sample and the next one, averaged 32 +/- 4 pM compared to 12 +/- 2 pM in the remaining period. In four volunteers somatostatin was infused in doses of 1.2, 2.4 and 4.8 pM/kg per min over three consecutive periods of 90 min, causing dose-dependent increments in plasma somatostatin levels of 7, 32 and 76 pM. In all volunteers and for all doses all gastric activity was completely inhibited. In the intestine phase 2 was abolished but phase 3 stimulated: during somatostatin infusion phase 3 occurred with an interval of 39 +/- 6 min. Motilin and PP levels were decreased. As the two lowest infusion doses caused increases in somatostatin levels that might be considered as physiological, somatostatin seems to have a physiological role in the regulation of the migrating motor complex. We propose that it facilitates the progressing of the activity front into the small intestine.     

Pancreatic polypeptide is not involved in the regulation of the migrating motor complex in man

The role of pancreatic polypeptide (PP) and motilin in the regulation of the migrating motor complex (MMC) was studied in normal subjects. Both plasma motilin and PP levels changed cyclically in the fasted state and were highest in the late phase II period preceding the activity front in the duodenum. A continental breakfast invariably disrupted the MMC and induced a fed pattern of motility. After the meal plasma motilin levels decreased whereas PP levels rose significantly. Infusion of pure porcine motilin during the fasted state induced an activity front and a rise in plasma PP levels. Infusion of bovine PP in doses producing plasma PP levels above the postprandial values neither induced an activity front nor prevented its occurrence. During PP infusion, however, plasma motilin levels were low, although the activity front was not inhibited. PP seems to have no clear role in the regulation of the motor component of the MMC of man. The role of motilin in the production of the activity front of the MMC is discussed.     

5-羟色胺和胃动素在狗小肠移行性复合运动调控中的作用

应用慢性植入小肠腔外应力传感器记录清醒狗小肠移行性复合运动（ＭＭＣ）。在颈外静脉和支配１０￣１５ｃｍ肠段的空肠动脉内分别放置－硅胶管以备灌流药物的取血样品用。本研究观察了静脉和动脉注射药物对小肠ＭＭＣ的影响及ＭＭＣ不同时相血浆５－羟色胺（５－ＨＴ）和胃动素的浓度变化。结果表明：（１）ＭＭＣ不同时相血浆５－ＨＴ和胃动素浓度呈周期性变化,５－ＨＴ峰值在胃动素峰值之前出现。血浆５－ＨＴ浓度在ＭＭＣⅡ相后     

Variations of plasma immunoreactive motilin, pancreatic polypeptide, gastrin and somatostatin along the duodenal motility cycle in the pig

The peripheral plasma concentrations of immunoreactive motilin, pancreatic polypeptide (PP), somatostatin and gastrin were measured in 7 pigs fasted to 24 h and subsequently fed a standard meal. Plasma motilin peaked during the last part of phase II activity of the migrating myoelectric complex (MMC) sequence (25.2 +/- 2.3 pM), the lowest value being recorded during phase I (10.6 +/- 1.5 pM) after a 24 h fast. Plasma motilin remained at a low level during the digestive pattern of duodenal activity, no fluctuation occurring when the first postprandial MMC recurred. At variance analysis, gastrin and PP were not released phasically with MMC in the fasting state, while at autocovariance both peptides tended to fluctuate during the MMC sequence with positive and negative peaks at regular intervals along MMC cycles. No variation of plasma somatostatin was observed in the fasting animals. These findings argue against a major role of circulating PP, gastrin and somatostatin-like components in the control of fasted and post absorptive duodenal motility in pigs while the role of motilin remains equivocal.     

Effect of neurotensin and neurotensin fragments on gastric acid secretion in man

The effect of intravenous infusion of neurotensin (NT) and NT-fragments on pentagastrin stimulated gastric acid secretion was investigated in healthy subjects. Neurotensin was infused in three doses (72, 144 and 288 pmol/kg per h). An N-terminal fragment (NT 1-8), a C-terminal fragment (NT 8-13) and an NT-analogue, substituted at the C-terminal tyrosine residue (Phe11-NT) were infused in two doses (72 and 144 pmol/kg per h). Concentrations of the infused peptides were measured in peripheral venous blood by radioimmunoassay. Plasma levels of NT 1-13, NT 1-8 and Phe11-NT increased in a dose-dependent manner; NT 1-13 to 50 (34-69), 78 (54-113) and 143 (112-242) pmol/l (medians and range) at 72, 144 and 288 pmol/kg per h, NT 1-8 to 405 (340-465) and 1215 (915-1300) pmol/l, and Phe11-NT to 200 (110-245) and 390 (250-410) pmol/l at 72 and 144 pmol/kg per h, respectively. Increases in plasma levels of NT 8-13 could not be detected during the infusion, suggesting that the fragment is rapidly metabolized in man. Neurotensin 1-13 inhibited gastric acid secretion in a dose-dependent manner and the decrease in gastric acid secretion was linearly related to plasma levels of NT 1-13. Neurotensin 1-8 and NT 8-13 inhibited gastric acid secretion only at 144 pmol/kg per h, while the analogue Phe11-NT had no effect. The results showed that the inhibition of gastric acid secretion produced by NT was dose-dependent and linearly related to circulating levels of NT, and that under physiological conditions this effect presumably is elicited by the C-terminal part of the peptide.     

Inhibition of human gastric lipase by intraduodenal fat involves glucagon-like peptide-1 and cholecystokinin

Seven healthy volunteers were intubated with two double lumen nasogastric tubes, one in the stomach, the other in the duodenum. This system allows simultaneous sampling of gastric juice and separate intraduodenal perfusion with a dietary fat (fish oil, 1269 kJ). Gastrin-17 was infused i.v. at a rate of 40 pmol/kg/h throughout the study. Gastric lipase was measured at 15-min intervals as activity (tributyrin) and as immunoreactivity (ELISA). Infusion of gastrin-17 resulted in a stable increase in the plasma concentration from a basal concentration of 8.3±0.8 pmol/l to 41.4±4.2 pmol/l. Perfusion with fat reduced gastric lipase activity from 24.2±5.3 to 7.2±2.5 kU/l (P<0.05), and immunoreactivity from 0.7±0.1 to 0.42±0.1 mg/l (P<0.05). After termination of fat perfusion, gastric lipase secretion increased again, though not reaching preinhibitory concentrations. During the intraduodenal perfusion with fat the plasma concentrations of glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) increased from 6.9±0.5 to 15.1±1.5 pmol/l (P<0.05) and from 1.2±0.4 to 3.8±0.9 pmol/l (P<0.05). This study reveals a negative effect of fat in the duodenum on gastric lipase secretion. This effect may be mediated by GLP-1 and/or CCK.     

Biological actions of peptide YY: effects on endocrine pancreas, pituitary-adrenal axis, and plasma catecholamine concentrations in the dog

The present study was designed to gather information on the biological activity of peptide YY (PYY) in conscious dogs. PYY was infused intravenously at a dose of 238 pmol/kg X h, and plasma concentrations of glucose, insulin, pancreatic polypeptide (PP), ACTH, cortisol and catecholamines (norepinephrine-NE; epinephrine-E; dopamine-DA) were subsequently measured. PYY significantly increased plasma insulin levels transiently without effect on plasma glucose, but decreased plasma PP levels during all infusion periods. PYY stimulated both plasma ACTH and cortisol secretion, and this action of PYY was also shared by PP, with PP being less potent in ACTH-cortisol release. PYY further elicited specific changes in plasma catecholamine concentrations, i.e. an increase of NE but not of E, which were in contrast to the effects of insulin-induced hypoglycemia. PP failed to alter plasma insulin and catecholamine concentrations. These results suggest that PYY can affect anterior pituitary hormone secretion, sympathetic nervous outflow and pancreatic endocrine activity in addition to its known actions on gastric and pancreatic secretion in the dog.     

Peripheral motilin administration stimulates feeding in fasted rats

Although the physiologic function of the gastrointestinal hormone motilin remains uncertain, plasma levels of this peptide vary with migrating myoelectric complexes (MMCs) in the small intestine. In the fed state, both MMCs and plasma motilin are suppressed. During fasting, cyclical peaks of motilin in plasma occur at the same time as Phase III of the MMC cycle occurs in the duodenum. This dependence of motilin concentrations in plasma on the feeding state of the animal prompted an investigation of the effects of motilin on feeding behavior. Intraperitoneal injection of motilin into fasted, but not fed, rats stimulated eating in a dose dependent manner. A significant stimulation of feeding was seen at doses of 5 and 10 μg/kg. Sated rats did not eat whether injected with motilin or vehicle. The feeding response to motilin was blocked by prior injection of the rats with naloxone, naltrexone, or pentagastrin. The dose response suppression of food intake by naloxone was similar in fasted animals treated with motilin or vehicle. Motilin may function as a hunger hormone during periods of fasting.     

Coordination of motilin and ghrelin regulates the migrating motor complex of gastrointestinal motility in Suncus murinus

Motilin and ghrelin are the gastrointestinal (GI) hormones released in a fasting state to stimulate the GI motility of the migrating motor complex (MMC). We focused on coordination of the ghrelin/motilin family in gastric contraction in vivo and in vitro using the house musk shrew (Suncus murinus), a ghrelin- and motilin-producing mammal. To measure the contractile activity of the stomach in vivo, we recorded GI contractions either in the free-moving conscious or anesthetized S. murinus and examined the effects of administration of motilin and/or ghrelin on spontaneous MMC in the fasting state. In the in vitro study, we also studied the coordinative effect of these hormones on the isolated stomach using an organ bath. In the fasting state, phase I, II, and III contractions were clearly recorded in the gastric body (as observed in humans and dogs). Intravenous infusion of ghrelin stimulated gastric contraction in the latter half of phase I and in the phase II in a dose-dependent manner. Continuous intravenous infusion of ghrelin antagonist (d-Lys3-GHRP6) significantly suppressed spontaneous phase II contractions and prolonged the time of occurrence of the peak of phase III contractions. However, intravenous infusion of motilin antagonist (MA-2029) did not inhibit phase II contractions but delayed the occurrence of phase III contractions of the MMC. In the in vitro study, even though a high dose of ghrelin did not stimulate contraction of stomach preparations, ghrelin administration (10(-10)-10(-7) M) with pretreatment of a low dose of motilin (10(-10) M) induced gastric contraction in a dose-dependent manner. Pretreatment with 10(-8) M ghrelin enhanced motilin-stimulated gastric contractions by 10 times. The interrelation of these peptides was also demonstrated in the anesthetized S. murinus. The results suggest that ghrelin is important for the phase II contraction and that coordination of motilin and ghrelin are necessary to initiate phase III contraction of the MMC.     

Interdigestive migrating contractions are coregulated by ghrelin and motilin in conscious dogs

During fasting, gastrointestinal (GI) motility is characterized by cyclical motor contractions. These contractions have been referred to as interdigestive migrating contractions (IMCs). In dogs and humans, IMCs are known to be regulated by motilin. However, in rats and mice, IMCs are regulated by ghrelin. It is not clear how these peptides influence each other in vivo. The aim of the present study was to investigate the relationship between ghrelin and motilin in conscious dogs. Twenty healthy beagles were used in this study. Force transducers were implanted in the stomach, duodenum, and jejunum to monitor GI motility. Subsequent GI motility was recorded and quantified by calculating the motility index. In examination 1, blood samples were collected in the interdigestive state, and levels of plasma ghrelin and motilin were measured. Plasma motilin peaks were observed during every gastric phase III, and plasma ghrelin peaks occurred in nearly every early phase I. Plasma motilin and ghrelin levels increased and decreased cyclically with the interdigestive states. In examination 2, saline or canine ghrelin was administered intravenously during phase II and phase III. After injection of ghrelin, plasma motilin levels were measured. Ghrelin injection during phases II and III inhibited phase III contractions and decreased plasma motilin levels. In examination 3, ghrelin was infused in the presence of the growth hormone secretagogue receptors antagonist [D-Lys3]-GHRP-6. Continuous ghrelin infusion suppressed motilin release, an effect abrogated by the infusion of [D-Lys3]-GHRP-6. Examination 4 was performed to evaluate the plasma ghrelin response to motilin administration. Motilin infusion immediately decreased ghrelin levels. In this study, we demonstrated that motilin and ghrelin cooperatively control the function of gastric IMCs in conscious dogs. Our findings suggest that ghrelin regulates the function and release of motilin and that motilin may also regulate ghrelin.     

Gastric and intestinal release of vasoactive intestinal polypeptide in the milk-fed lamb

Vasoactive intestinal polypeptide (VIP) has been proposed as the neurotransmitter of the atropine-resistant relaxation of gastric structures in the lamb. To examine this proposal VIP concentrations in plasma from arterial, gastric venous and intestinal venous blood were measured in healthy conscious lambs before, during and after teasing with, and sucking of milk. Basal arterial plasma VIP concentrations were undetectable (less than 3 pmol/l) and remained so during and after feeding. Before feeding VIP was detected in only 2 of 12 gastric venous plasma samples (5 and 13 pmol/l). During teasing with food there were increments in VIP of 19 +/- 4 pmol/l and during feeding of 27 +/- 5 pmol/l. VIP concentration in gastric venous plasma rapidly returned to fasting levels after cessation of sucking. In contrast VIP in the intestinal venous plasma did not rise during teasing or upon commencement of sucking but a peak increment of 34 +/- 6 pmol/l occurred at 5 min after cessation of feeding. The results are consistent with the hypotheses that VIP is released in anticipation of and during sucking from inhibitory neurones involved in relaxation of gastric structures and that intestinal release of VIP is a consequence of entry of digesta into the small intestine.     

The effect of atropine on bombesin and gastrin releasing peptide stimulated gastrin, pancreatic polypeptide and neurotensin release in man

The effects of 1-h infusions of bombesin and gastrin releasing peptide (GRP) at 50 pmol/kg per h and neurotensin at 100 pmol/kg per h on gastrin, pancreatic polypeptide (PP) and neurotensin release in man were determined following either saline or atropine infusion (20 micrograms/kg). Bombesin produced a rise in plasma neurotensin from 32 +/- 6 to 61 +/- 19 pmol/l and of PP from 26 +/- 8 to 36 +/- 7 pmol/l. There was a further rise of plasma PP to 50 +/- 13 pmol/l after cessation of the infusion. GRP had no significant effect on plasma neurotensin, but compared to bombesin, produced a significantly greater rise in plasma PP from 34 +/- 6 to 66 +/- 19 pmol/l during infusion. There was no post-infusional increase. At this dose, GRP was as effective as bombesin in releasing gastrin, although unlike bombesin its effect was enhanced by atropine. Neurotensin produced a rise in plasma PP from 17 +/- 4 to 38 +/- 8 pmol/l. Atropine blocked the release of PP during GRP and neurotensin infusion. Atropine had no effect on neurotensin or PP release during bombesin infusion, but did block the rise in plasma PP following bombesin infusion. We conclude that, in contrast to meal-stimulated neurotensin release, bombesin-stimulated neurotensin release is cholinergic independent. Despite structural homology, bombesin and GRP at the dose used are dissimilar in man in their actions and sensitivity to cholinergic blockade.     

Effect of stimulation of the vagus nerves and vagotomy on myoelectric activity of small bowel

Experiments have been done on conscious dogs (6 animals) to study vagal influences on small bowel motility. First group (3 dogs) was prepared with gastric and esophageal fistulas, the second group (3 dogs) with gastric fistulas. Both groups had monopolar silver electrodes placed along small bowel. Stimulation of vagus with sham feeding (SF) increased MMC period of about 21%. Insulin and 2DG infused intravenously increased MMC period at lower dose range and in high doses induced fed-like pattern of motility. Supradiaphragmatic vagotomy done in the second group animals does not change significantly fasted as well as fed motility pattern. These data suggest that central and peripheral vagal input is required for inhibition MMC activity and development fed motility pattern.     

Variations in plasma motilin, somatostatin, and pancreatic polypeptide concentrations and the interdigestive myoelectric complex in dog

We have looked at the plasma concentrations of motilin, pancreatic polypeptide (PP), and somatostatin (STS) during the various phases of the interdigestive motor complex (IDMC) in dogs. As expected, motilin cyclical increase was always associated with the phase III of the IDMC. Statistical analysis of PP variations revealed a significant rise 10 min before duodenal phase III; however, in individual animals, this relationship was inconsistent. Although a dose-related increase in PP blood levels was induced by administration of synthetic canine motilin (0-200 ng kg-1 iv), fasting plasma levels of PP were not correlated with the concentrations of circulating endogenous motilin. After truncal vagotomy, while motilin release and the intestinal motility pattern remained unaltered, the phase III associated cyclical increases of PP disappeared. Infusion of physiological amounts of PP (1 microgram kg-1 h-1 for 3 h) mimicking the postprandial release failed to reproduce a fed pattern type of intestinal motility and of motilin secretion. No statistical correlation could be established between STS plasma levels and the motor activity of the intestine. STS plasma levels were not correlated with circulating concentrations of motilin and the exogenous administration of physiological doses of synthetic canine motilin failed to modify STS plasma levels. Morphine (200 micrograms kg-1 iv) stimulated only the release of motilin. These data suggest that the role played by circulating concentrations of PP and STS in the control of the IDMC in dog is at most minimal.     

The renal actions of oxytocin in the conscious rat

The renal actions of oxytocin were studied in the conscious unrestrained rat infused with 0.077 M saline at a rate of 150 microliters/min. During the control period volume and sodium excretion reached stable equilibria, the rates being equal to those infused. Administration of oxytocin at 200 pmol/min produced plasma oxytocin levels of 26.0 +/- 2.1 pmol/l and caused a significant diuresis and natriuresis. Renal responses could also be seen with a lower dose of 30 pmol/min which produced plasma levels of 5.1 +/- 0.5 pmol/l while a dose of 15 pmol/min which produced no significant increase in the plasma oxytocin had no renal effect. It appears that oxytocin has a natriuretic action in concentrations within the physiological range.     

Effects of pancreatic polypeptide on the pancreatic exocrine secretion stimulated by secretin and cholecystokinin in the conscious pig

Fourteen castrated male Large White pigs, weighing 42.5 +/- 1.0 kg, were fitted with pancreatic and duodenal fistulae for pancreatic secretion studies. Moreover, catheters were placed in a carotid artery for blood sampling and in a jugular vein for peptide infusion. Pancreatic juice was automatically restituted to the animals and continuously sampled for analysis on experimental days. Following an 8-day recovery period, perfusion studies were performed after an overnight fast. After a 30-min basal period, sustained pancreatic flow and protein output were obtained and maintained throughout the assay with secretin (36 pmol/kg/h) and CCK-8 (600 pmol/kg/h) infusion. Then, 200, 400, 600, 800 or 1200 pmol/kg/h of porcine pancreatic polypeptide (PP) were infused for 60 min. Secretin + CCK infusion was continued for 1 h after PP infusion was stopped. Each dose of PP was given on a separate day. Neither pancreatic flow nor bicarbonate output were affected whatever the dose of infused PP. On the contrary, protein concentration and output decreased with the lowest dose of PP (200 pmol/kg/h) and the diminution was more pronounced with the other doses. With 600 pmol/kg/h as well as with 800 and 1200 pmol/kg/h of PP, pancreatic protein output fell to about 20% of values obtained with secretin + CCK. Plasma levels of PP were below or similar to postprandial values for 200, 400 and 600 pmol/kg/h and they were significantly larger with 800 and 1200 pmol/kg/h. Protein concentration and output returned to values obtained with secretin + CCK infusion after cessation of PP infusion. In conclusion, porcine PP given in physiological doses to the pig decreases pancreatic protein output whereas pancreatic flow remains unaffected.     

Effects of pancreatic polypeptide on biliary flow and bile acid secretion stimulated by secretin and cholecystokinin in the conscious pig

Fourteen castrated male Large White pigs, weighing 42.5 +/- 1.0 kg, were fitted with biliary and duodenal fistulae for biliary secretion studies. Furthermore, catheters were placed in a carotid artery for blood sampling and in a jugular vein for peptide infusion. Bile was automatically restituted to the animals and continuously sampled for analysis on experimental days. Following an 8 day recovery period, infusion studies were performed after an overnight fast. After a 30 min basal period, sustained biliary flow and bile acid output were obtained and maintained throughout the assay with secretin (36 pmol/kg/h) and CCK-8 (600 pmol/kg/h) infusion. Then, 200, 400, 600, 800 or 1200 pmol/kg/h of porcine pancreatic polypeptide (PP) were infused for 60 min. Secretin plus CCK infusion was continued for 1 h after PP infusion was stopped. Each dose of PP was given on a separate day. Biliary flow was not affected by PP except for the dose of 400 pmol/kg/h. On the contrary, bile acid concentration and output decreased with the lowest dose of PP (200 pmol/kg/h). As soon as the first dose of PP was infused, bile acid concentration and output fell to about 60% of values obtained with secretin plus CCK. Plasma levels of PP were below or similar to postprandial values for 200, 400 and 600 pmol/kg/h and they were significantly larger with 800 and 1200 pmol/kg/h. Bile acid concentration and output did not return to values obtained with secretin plus CCK infusion after cessation of PP infusion. In conclusion, porcine PP given in physiological doses to the pig decreases bile acid output whereas biliary flow remains unaffected.     

Effects of neurotensin on small bowel propulsion in intact and vagotomized rats

The effects of intravenous infusion of neurotensin on small bowel motility was studied in conscious rats. During 1 h a standardized test meal of glucose, polyethyleneglycol (PEG) 3000, phenol red and ¹²⁵I-labelled polyvinylpyrrolidone was administered via a permanent gastric catheter and simultaneously the bile-excreted radiopharmaceutic ⁹⁹Tc^m-Solco-HIDA was infused intravenously. Immediately after the infusions the gastrointestinal specimen was excised and examined for distribution of radioactivity. Both doses of neurotensin (0.1 and 0.3 μg · kg^?1 · h^?1) resulted in an increase in the neurotensin-like immunoreactivity (NTLI) of plasma to levels similar to that found after a fatty meal. Concurrently the small bowel transport pattern was changed from an interdigestive state to one similar to that found after a meal. In animals not receiving the gastric test meal, neurotensin (0.1–0.5 μg · kg^?1 · h^?) had no effect on motility. Infusion of the gastric test meal alone did not change the interdigestive motility or the NTLI value. This indicates that the presence of gastric infusates potentiates the effect of neurotensin on small bowel motility. The motility response to neurotensin did not differ between intact and vagotomized animals. This contrasts to earlier findings that the small bowel motility response to a fatty meal is dependent on intact vagal function. Thus, a difference in the mechanism responsible for the motility responses between a fatty meal and neurotensin exists. In view of this finding it seems reasonable to assume that neurotensin cannot be the only factor responsible for the shift in motility found after a fatty meal.     

The role of vagal integrity in gastrin releasing peptide stimulated gastroenteropancreatic hormone release and gastric acid secretion

The role of the vagus nerve in the control of gastrin releasing peptide (GRP) stimulated gastroenteropancreatic hormone release and gastric acid secretion was investigated in four conscious gastric fistula dogs using a technique of bilateral cryogenic vagal blockade. A 90-min infusion of GRP at a dose of 400 pmol X kg-1. h-1 produced significant elevations in plasma levels of gastrin, motilin, GIP, enteroglucagon, insulin, pancreatic glucagon, pancreatic polypeptide and VIP. Vagal blockade reversibly inhibited the rise of plasma PP and significantly blunted the elevation of plasma VIP. However, the GRP stimulated response of the other hormones investigated was not modified by vagal blockade. Similarly, the substantial secretion of gastric acid observed with GRP was not influenced by vagal blockade. Thus GRP acts predominantly via mechanisms which are independent of vagal integrity, findings that are in support of a major role for the local neuromodulation of hormone release and gastric acid secretion.     

Somatostatin release induced by gastrin-releasing peptide in man. Effect of proximal gastric vagotomy and cholinergic blockade

The influence of intragastric pH on the basal release of somatostatin has been studied in healthy controls and in duodenal ulcer patients. In addition the somatostatin response to gastrin-releasing peptide infusion has been evaluated both regarding the effect of intragastric pH and the influence of vagal innervation and muscarinic blockade. No difference was found in basal blood levels, when changing the intraluminal pH, although a slightly higher basal somatostatin concentration was noticed in patients with duodenal ulcer disease. Neither proximal gastric vagotomy nor cholinergic blockade had any effect on basal somatostatin concentrations. GRP infused in stepwise increasing doses from 20 pmol/kg/h to 400 pmol/kg/h induced a small but significant response. This effect of GRP was most evident, when the stomach was perfused with 0.1 M HCl. The small, somatostatin response to GRP infusion was not influenced by vagal denervation of the parietal cell area, neither by cholinergic blockade. Despite the previously observed effects of vagotomy and cholinergic blockade on gastrin release induced by GRP, a corresponding inverse effect on somatostatin is not apparent.