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Background: Increased gastric emptying and defective action of endogenous cholecystokinin (CCK), that is known to inhibit this emptying, have been implicated in the pathogenesis of duodenal ulcer (DU). The aim of this double blind study was to assess whether CCK and somatostatin participate in the impairment of gastric motility in active DU patients before and after Helicobacter pylori eradication., Methods: Tests were undertaken in 10 DU patients without or with elimination of the action of endogenous CCK using loxiglumide, a selective CCK-A receptor antagonist, before and 4 weeks after eradication of H. pylori with 1 week triple therapy that resulted in healing of all DUs tested. The gastric emptying rate after feeding was determined using the 13C-acetate breath test. Before each test, samples of gastric juice were obtained by aspiration using a nasogastric tube for determination of somatostatin using specific radioimmunoassay., Results: Prior to H. pylori eradication gastric emptying half-time was 31 +/- 6 min in placebo-treated DU patients and this emptying rate was not significantly affected in tests after pretreatment with loxiglumide (10 mg/kg i.v.). Following eradication of H. pylori, in tests with placebo gastric emptying half-time was significantly longer (48 +/- 9 min) compared to that prior to H. pylori eradication. Pretreatment with loxiglumide in H. pylori eradicated DU patients significantly enhanced the gastric emptying rate with an emptying half-time of only 33 +/- 4 min. Eradication of H. pylori resulted in a significant increase in somatostatin concentration in gastric juice and loxiglumide significantly reduced this luminal somatostatin in H. pylori-eradicated subjects compared to values before anti-H. pylori therapy., Conclusions: 1) H. pylori infection in DU patients is accompanied by enhanced gastric emptying and reduction in luminal release of somatostatin; 2) the failure of loxiglumide to affect gastric emptying in H. pylori-infected DU patients might be attributed, at least in part, to the failure of endogenous CCK to control gastric motility due to deficient release of somatostatin; and 3) H. pylori-infected patients appear to exhibit a deficient somatostatin release by endogenous CCK that can be reversed by the eradication of H. pylori indicating that both CCK and somatostatin may contribute to normalization of gastric emptying following H. pylori eradication in DU patients.

Objective: Cholecystokinin (CCK) is able to protect gastric mucosa against acute injury in experimental animals but little is known about the role of this hormone in maintaining mucosal integrity in humans. This double-blind, placebo controlled study was performed in 16 healthy volunteers. It describes the effects of CCK-8 infused intravenously (i.v.) at physiological doses and endogenous CCK released by intraduodenal (i.d.) oleate on gastric mucosal damage, as brought about by ethanol without or with pretreatment with loxiglumide, a selective CCK-A receptor antagonist., Methods: CCK-8 was infused i.v. 30 min before and throughout the study or i.d. oleate was instilled through a separate duodenal tube. Thirty minutes after the start of i.v. infusion of CCK or i.d. oleate instillation, 100 ml of 50% ethanol spray was applied to the gastric mucosa using an endoscope. Gastroscopy was performed and mucosal lesions were quantified using modified Lanza score. Gastric biopsies were taken from oxyntic mucosa for histological evaluation and gastric content was aspirated for radioimmunoassay of somatostatin., Results: In placebo-treated subjects ethanol caused endoscopic damage, with an average score of 2.8+/-0.2. Histologically, a widespread disruption of surface epithelium and deep hemorrhagic necrotic lesions were observed. Pretreatment with CCK or i.d. oleate markedly reduced the endoscopic lesion score to 0.7+/-0.1 and 0.3+/-0.1, respectively, and in both cases this reduction was accompanied by a significant rise in plasma CCK. Histologically, surface epithelium was still disrupted but deep necrotic lesions were absent. Gastric content collected before and after CCK or oleate showed a several-fold increase of luminally released somatostatin., Conclusions: Pretreatment with loxiglumide abolished the protective effects of i.v. CCK-8 and i.d. oleate on mucosal lesions induced by ethanol and prevented the rise in intragastric somatostatin, but failed to affect the increments in plasma CCK. Endogenous CCK plays a physiological role in the maintenance of mucosal integrity. This occurs through activation of CCK-A receptors and is associated with an increased gastric luminal release of somatostatin.

This study was designed to determine the role of nitric oxide in gallbladder (GB) contractions in men. The studies were performed in 10 young healthy male volunteers. GB emptying was examined by ultrasonography under basal conditions and after intravenous infusion of cholecystokinin (CCK8; 12.5 pmol/kg x h) or yolk intake in tests without (saline) and with intravenous infusion of NG-monomethyl-L-arginine (L-NMMA; 4.0 micromol/kg x h) and/or L-arginine (1 mmol/kg x h). The plasma CCK level was determined by radioimmunoassay. It was found that the basal GB volume was about 27 +/- 3 ml, and after CCK8 infusion or yolk meal this volume was reduced within about 30 min by about 93 and 80%, respectively. Pretreatment with L-NMMA caused reduction of the baseline volume by about 15% and significantly augmented the GB emptying induced by CCK8 infusion and yolk intake. L-Arginine alone failed to affect basal or stimulated (CCK or yolk) emptying of the GB, but when combined with L-NMMA, it reversed the enhancement of GB contraction caused by L-NMMA. The basal plasma CCK level was 1.2 +/- 0.3 pmol/l and rose to 7.9 +/- 2.1 pmol/l with CCK8 infusion and to 4.7 +/- 1.8 pmol/l after yolk meal. No significant change in plasma CCK levels was observed in tests with L-NMMA and/or L-arginine. We conclude that under physiological conditions, the GB contractile activity is regulated predominantly by CCK, but endogenous nitric oxide has a tonic relaxing influence on this activity.

Helicobacter pylori (Hp) infection may be associated with duodenal ulcer (DU) and accompanied by increased release of gastrin and deficiency of somatostatin (S-S) but the mechanisms of these changes in DU patients after eradication of Hp have been little studied. Cholecystokinin (CCK) has been implicated in the feedback control of gastric acid secretion in healthy subjects but its contribution to secretory disorders in DU patients has been little examined. This study, therefore, investigated whether CCK participates in the impairment of postprandial gastrin release and gastric acid secretion in active DU patients. Tests were undertaken in 10 DU patients without or with elimination of the action of endogenous CCK using loxiglumide (LOX), a selective CCK-A receptor antagonist, before and 4 wk. after eradication of Hp with triple therapy (omeprazole, amoxycillin and bismuth). In Hp positive DU patients, the postprandial acid secretion (measured by continuous intragastric pH monitoring) was accompanied by a pronounced increment in plasma gastrin with negligible increase of intraluminal release of S-S. The administration of LOX in these patients did not affect significantly the postprandial pH profile and the rise in plasma gastrin. After eradication of Hp the median postprandial intragastric pH increased to about 4.3 (compared to 3.5 before the Hp eradication); the postprandial gastrin concentration was reduced by about 40%, while luminal release of S-S was increased 2 folds. The administration of LOX resulted in significantly greater decrease in median pH (3.1) and higher rise in postprandial plasma gastrin in these patients. Also the postprandial plasma S-S showed a small, but significant decline (by about 25%) as compared to that in placebo treated patients. This study provides evidence that: (1) Hp infection in DU patients is accompanied by enhanced gastrin release and the reduction in luminal release of S-S; (2) The failure of LOX to affect gastric secretion and plasma gastrin DU Hp infected patients could be attributed, at least in part, to the failure of endogenous CCK to control gastric acid secretion via release of S-S; (3) Hp infected patients appear to exhibit a deficiency of S-S release that can be reversed by the eradication of Hp indicating that both peptides may contribute to the acceleration of the ulcer healing following Hp eradication in DU patients; (4) The test with LOX and gastric luminal S-S assay may be useful in identification of Hp positive DU patients with CCK-mediated impaired feedback control of gastric secretion and deficiency of S-S caused by Hp infection.

Helicobacter pylori infection may be associated with duodenal ulcer (DU) and accompanied by enhanced gastrin release but the mechanism of this H pylori related hypergastrinaemia in DU patients is unclear. Cholecystokinin (CCK) has been implicated in the feedback control of gastrin release and gastric acid secretion in healthy subjects. This study therefore investigated if CCK participates in the impairment of postprandial gastrin release and gastric secretion in six DU patients. Tests were undertaken with and without elimination of endogenous CCK by loxiglumide, a selective CCK-A receptors antagonist, before and after eradication of H pylori with triple therapy (omeprazole, amoxicyllin, bismuth). In H pylori positive DU patients, the post-prandial decline in pH (with median pH 3.5) was accompanied by a pronounced increment in plasma gastrin but the administration of loxiglumide did not affect significantly this postprandial rise in plasma gastrin and gastric pH profile. After eradication of H pylori, the plasma gastrin concentration was reduced while the median postprandial pH was significantly increased (median pH 4.3). The administration of loxiglumide resulted in significantly greater increase in postprandial plasma gastrin and greater decrease in pH (median pH 3.1) in these patients. This study shows that (a) infection with H pylori is accompanied by an enhanced gastrin release and gastric acidity in DU patients, (b) the failure of loxiglumide to affect plasma gastrin or gastric acid secretion in H pylori infected DU patients could be attributed, at least in part, to the failure of endogenous CCK to control gastrin release and gastric secretion by releasing somatostatin, and (c) the test with loxiglumide may be useful in the identification of patients with impaired feedback control of gastrin release and gastric secretion resulting from infection with H pylori.

Objective: In healthy subjects a gastric meal at low pH inhibits gastric acid secretion, possibly by reducing gastrin release, whereas duodenal ulcer (DU) patients have been reported to show a lack of this low pH inhibition of gastric secretion., Methods: The intragastric pH profiles were measured in seven healthy subjects and seven DU patients after meals of pH 6.5 and 3.0 without or with pretreatment with loxiglumide (1.2 g orally), a selective antagonist of type-A cholecystokinin (CCK) receptors. During all tests (30 min before and 30, 60, and 90 min after each meal) plasma gastrin, CCK, and somatostatin were determined by specific radioimmunoassays., Results: In healthy subjects a standard meal at pH 6.5 and 3.0 resulted in median 3-h intragastric pH of 3.8 and 2.8, respectively. In DU patients under the same conditions the pH 6.5 meal resulted in median 3-h intragastric pH of 3.4, and the acidified meal in pH 2.2. After pretreatment with loxiglumide the median pH after both meals was significantly lower in healthy controls but not in DU patients. After the pH 6.5 meal, in healthy subjects the plasma gastrin rose by 57%, CCK by 177%, and somatostatin by 39%, and in DU patients by 152%, 367%, and 125%, respectively. Pretreatment with loxiglumide led to a marked increase in plasma gastrin response to the pH 6.5 meal only in healthy controls and not in DU subjects, and it was accompanied by a significant increase in plasma CCK and a decrease in plasma somatostatin. The pH 3.0 meal resulted in a significantly smaller rise in plasma gastrin and a higher increase in CCK and somatostatin in both groups; again, after treatment with loxiglumide only healthy controls and not DU patients showed significant increase in plasma gastrin level., Conclusions: Acidification of meals results in the reduction of plasma gastrin and increase in plasma CCK and somatostatin in both healthy subjects and DU patients. DU patients differ from healthy subjects by virtually unchanged plasma gastrin response to a meal after CCK antagonism with loxiglumide, suggesting a defect in both gastric acid and gastrin inhibition by CCK in these patients.

Unlike the stimulation of gastric acid secretion, which clearly involves the release of gastrin, the mechanisms of inhibition of this secretory process are poorly defined although recent studies in animals with the use of highly selective cholecystokinin (CCK) antagonists indicate that CCK may play a crucial role in this inhibition. Duodenal ulcer patients (DU) differ from healthy controls by higher total acid secretory rates and diminished inhibition of acid secretion. Several possible pathomechanisms of the abnormal gastric secretory function in DU patients were previously proposed. The deficiency of CCK-induced gastric inhibition in DU patients together with the somatostatin hypothesis appear to be attractive, particularly so the suggestion that a deficiency of somatostatin activity exists in DU patients.

Background: Exogenous cholecystokinin (CCK) is known to effect gastric secretory and motor functions but its physiological role in the control of these functions in healthy subjects and duodenal ulcer (DU) patients is unknown., Methods and Subjects: In this study involving four series of young healthy normal and DU subjects, the gastric secretory tests were performed under basal conditions and following stimulation by modified sham-feeding (MSF), i.v. infusion of caerulein, gastrin releasing peptide (GRP) or pentagastrin (p-gastrin) (series A), after 500 ml of standard meal without or with addition of 15% soybean oil (series B) or acidification of meal to pH 2.5 (series C), and finally after eradication of Helicobacter pylori (HP) (series D). Studies were carried out without or with the pretreatment with placebo or loxiglumide, a specific antagonist of type A CCK receptors. In series A, the gastric secretion obtained by aspiration technique was measured after secretagogues (MSF, caerulein, GRP or p-gastrin), whereas in series B, C, and D intragastric pH was measured before and after test meal and plasma gastrin, CCK and somatostatin were assayed by specific radioimmunoassays., Results: In healthy subjects, MSF increased gastric acid outputs to about 36% of p-gastrin maximum and treatment with loxiglumide failed to affect this secretion. Standard meal enhanced acid output to about 50% of p-gastrin maximum and raised plasma levels of gastrin, CCK but not somatostatin. The pretreatment with loxiglumide resulted in further increase both in gastric acid secretion and plasma gastrin and CCK, while somatostatin level was significantly reduced. Infusion of graded doses of caerulein or GRP resulted in dose-dependent stimulation of gastric acid secretion reaching, respectively, 35% and 25% of p-gastrin maximum. When loxiglumide was added, the acid responses to caerulein and GRP were further increased by 2-3 folds, attaining a peak similar to the p-gastrin maximum. Administration of loxiglumide resulted in a significant increase in plasma gastrin and CCK responses to GRP, whereas plasma somatostatin was not significantly altered. Addition of fat to standard meal prolonged gastric emptying of this meal by about 50% both in healthy subjects and DU patients (series B). Fat in healthy subjects significantly increased and prolonged intragastric pH after the meal while reducing the increments in plasma gastrin and enhancing plasma CCK without alteration of plasma somatostatin. Pretreatment with loxiglumide significantly reduced postprandial pH from control 4.8 to 2.5 and reversed the changes in pH caused by addition of fat. The increments in plasma gastrin and CCK were markedly augmented, whereas those of somatostatin were attenuated. DU patients showed lower postprandial pH (3.0) in tests with or without fat and higher increments in plasma gastrin. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin or CCK. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin. Intragastric application of standard meal of pH 3.0 in healthy subjects and DU patients (series C) resulted in significantly lower median 3 h intragastric pH as compared to that after meal of pH 6.5. After pretreatment with loxiglumide, the median pH after meals of both pHs was significantly lower in healthy subjects but not in DU patients. This reduction in pH was accompanied by more pronounced increase in plasma gastrin response to a meal of pH 6.5 only in healthy controls but not in DU subjects and by a significant increase in plasma CCK and decrease in plasma somatostatin.

Background: Exogenous cholecystokinin (CCK) is known to affect gastric motor and secretory activities, but its physiologic role in the control of gastric functions is unknown., Methods: In this study involving 10 young healthy subjects and 10 duodenal ulcer (DU) patients, 500 ml of a standard meal without or with addition of 15% soybean oil was given, and the gastric emptying rate and the pH profile and plasma levels of gastrin, CCK, pancreatic polypeptide (PP), and somatostatin were determined in separate tests with placebo or with antagonism of type-A CCK receptors (loxiglumide, 1200 mg orally)., Results: In healthy controls and DU patients the emptying half-time was 44 and 34 min, respectively, and the addition of oil prolonged the emptying by about 50%. Pretreatment with loxiglumide significantly reduced fat-induced retardation of gastric emptying in both healthy controls and DU patients. A standard meal in healthy subjects resulted in an immediate rise in median gastric pH to about 6.0, and this was followed by gradual decrease within about 3 h to premeal values of about 2.0. After the meal, plasma gastrin rose by 57%, CCK by 177%, PP by 100%, and somatostatin by 39%. Addition of fat significantly attenuated and prolonged the pH decrease after the meal while reducing the increment in plasma gastrin and enhancing plasma CCK and PP levels. Loxiglumide significantly reduced the median postprandial pH (from control 4.8 to 2.5) and reversed the changes in the pH profile caused by the addition of fat. The increments in plasma gastrin and CCK were markedly augmented, whereas those of somatostatin and PP were significantly attenuated. DU patients showed lower postprandial pH (3.0) in tests with or without fat and higher increments in plasma gastrin. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin in DU patients., Conclusions: These results indicate that endogenous CCK released by a fatty meal delays gastric emptying and inhibits gastric acid and plasma gastrin responses in healthy subjects, but in DU patients the inhibitory effect of CCK is less pronounced, suggesting a defect in the action of this hormone on gastrin release and gastric acid secretion.

In this study, a selective antagonist of cholecystokinin (CCK)-A receptors, loxiglumide, was used to evaluate the role of CCK in the control of the release of gastrin and pancreatic hormones (insulin, glucagon, pancreatic polypeptide (PP), and somatostatin) after stimulation with exogenous CCK and ingestion of a standard liquid mixed meal in healthy humans. Exogenous CCK-8, which induced a small but significant increase in gastric acid secretion, resulted in dose-dependent increments in plasma PP levels without significant changes in plasma levels of insulin, glucagon, or somatostatin. Pretreatment with loxiglumide resulted in a marked increase in CCK-induced gastric acid secretion and abolished the increments in plasma PP without alteration of plasma insulin, glucagon, or somatostatin levels. Ingestion of the liquid meal resulted in an immediate rise in intragastric pH from basal values of about 2 to pH6 lasting 90-120 min, and this was accompanied by significant increments in plasma gastrin, insulin, glucagon, PP, and somatostatin. Administration of loxiglumide (1200 mg orally) caused a reduction in the postprandial intragastric pH and the two- to three-fold increase in plasma gastrin. Plasma insulin and glucagon levels in tests with loxiglumide tended to increase, probably owing to accelerated gastric emptying, whereas plasma PP and somatostatin were significantly reduced. This study provides evidence that CCK exerts an inhibitory effect on gastric acid secretion and plasma gastrin release as well as a stimulatory influence on the release of PP and somatostatin via CCK-A receptors but does not influence directly insulin or glucagon secretion in man.

This study was designed to determine the role of cholecystokinin in the control gastric acid secretion in men using loxiglumide, a specific cholecystokinin receptor blocker. Three groups of healthy subjects (A, B, and C) were used; group A--for studies with postprandial gastric secretion, group B--for studies with exogenous gastric secretagogues and group C--for 12 hour intragastric pH-metry. Cephalic phase stimulated by modified sham feeding in group A subjects increased gastric acid secretion to about 50% of pentagastrin maximum and the treatment with loxiglumide in a standard dose (20 mumol/kg iv loading dose plus infusion of 20 mumol/kg/h afterwards) failed to affect this secretion. Gastric acid response to a 5% peptone meal instilled intragastrically greatly enhanced gastric acid secretion and plasma gastrin concentration but the addition of loxiglumide in the standard dose resulted in further increase in both gastric acid and plasma gastrin responses to peptone meal. Infusion of caerulein in gradually increasing doses (15-120 pmol/kg/h) and gastrin releasing peptide (25-200 pmol/kg/h) resulted in a dose dependent stimulation of gastric acid secretion reaching about 35% and 25% of maximum attained with pentagastrin. When loxiglumide was added in a standard dose, the acid responses to caerulein and gastrin releasing peptide were further increased two to three fold attaining the peak reaching, respectively, about 100% and 50% of pentagastrin maximum. In group C subjects, 12 hour pH-metry revealed the usual increase in gastric pH after each meal in tests with placebo. Loxiglumide (1200 mg tablets tid, po) resulted in significantly lower pH after each meal and this was accompanied by significantly higher gastrin responses than in placebo tests. We conclude that cholecystokinin released by peptone meal, ordinary meals or gastrin releasing peptide exerts a potent inhibitory influence on gastric acid secretion and gastrin release in men and this inhibition involves subtype A cholecystokinin receptors.

This study was designed to determine the involvement of cholecystokinin (CCK) in the control of gastric acid secretion in men using loxiglumide, a specific CCK-receptor antagonist. Two groups of healthy subjects (A and B) were used: group A for studies of postprandial gastric secretion and group B for studies with exogenous gastric secretagogues. The cephalic phase activated by modified sham feeding (MSF) in group A subjects increased gastric acid secretion to about 36% of pentagastrin maximum, but treatment with loxiglumide in a standard dose (20 mumol/kg i.v. loading dose plus infusion of 20 mumol/kg/h afterwards) failed to affect this secretion. A 5% peptone meal instilled i.g. (to mimic the gastrointestinal phase) greatly enhanced gastric acid secretion and plasma gastrin concentration, but the addition of loxiglumide in a standard dose resulted in a further increase in both gastric acid and plasma gastrin responses to the peptone meal. Plasma somatostatin response to the peptone meal was significantly reduced by loxiglumide. Infusion of cerulein in gradually increasing doses (15-120 pmol/kg/h) and gastrin-releasing peptide (GRP) (25-200 pmol/kg/h) resulted in dose-dependent stimulation of gastric acid secretion, reaching about 35 and 25% of the maximum attained with pentagastrin. When loxiglumide was added the acid responses to cerulein and GRP were further increased by two- to threefold, attaining a peak similar to the pentagastrin maximum. Administration of loxiglumide resulted in a significant increase in plasma gastrin response to GRP, whereas plasma somatostatin was not significantly altered by loxiglumide.(ABSTRACT TRUNCATED AT 250 WORDS)

Postprandial pancreatic secretion results from the interaction of neural and hormonal factors but their contribution to the net postprandial secretion is unknown. Recent description of highly specific and potent cholecystokinin (CCK) receptor antagonists allows the determination of the physiological role of CCK in the postprandial pancreatic secretion. In six dogs with chronic pancreatic fistulae, the blockade of CCK receptors by non-peptidal agent (L-364,718) caused little change in basal pancreatic secretion, but decreased significantly (p less than 0.05) by about 60% the pancreatic protein response to meat feeding and virtually abolished the pancreatic responses to CCK-8 and bombesin. The pancreatic protein responses to pentagastrin, reaching about 37% of CCK maximum, was also significantly reduced but this effect was less pronounced than that observed in tests with CCK-8 or bombesin stimulation. In contrast, cholinergically stimulated pancreatic secretion, reaching about 40% of CCK maximum, was unaffected by L-364,718. Cholecystokinin antagonism also failed to affect the postprandial and bombesin induced increments in plasma CCK and gastrin concentrations, but significantly reduced the PP responses to CCK-8 bombesin and meat feeding possibly as a result of the removal of the CCK mediated release of PP. We conclude that CCK plays a crucial role in the mediation of the postprandial and bombesin induced pancreatic secretion and in the PP release.

The postprandial contractions of the gall bladder result from the interaction of neurohormonal factors but their relative contribution is unknown. This study was designed to determine the role of cholecystokinin (CCK) in gall bladder contractions using a highly selective and potent CCK-receptor antagonist, CR-1505 (loxiglumide) in healthy men either infused with exogenous CCK in graded doses (1.56-50 pmol/kg/h) or subjected to modified sham feeding (MSF) and ordinary feeding tests. The gall bladder volume measured by real time ultrasonography showed dose dependent decrease in the gall bladder volume in 10 subjects when CCK8 was infused iv in graded doses reaching about 15% at 1.56 pmol/kg/h and 91% at 50 pmol/kg/h. Close correlation between the decrease in gall bladder volume and the dosage of CCK or the increments in plasma CCK-bioactivity was observed. After pretreatment with loxiglumide, CCK resulted in similar increments in plasma CCK-bioactivity but failed to affect the gall bladder volume at CCK doses up to 6.25 pmol/kg/h and caused only 53% reduction at 50 pmol/kg/h. Modified sham feeding and real feeding reduced the volume of gall bladder by 20% and 70%, respectively and loxiglumide decreased these values to 15% and 30%, respectively. This study provides evidence that loxiglumide is highly potent and selective CCK antagonist and that endogenous CCK plays an important role both in the postprandial contractions of gall bladder.

The role of gut hormones, such as secretin and CCK, in the stimulation of pancreatic secretion by duodenal HCl or oleate and by meat feeding has been studied in conscious dogs before and after pretreatment with atropine and somatostatin. Plasma hormones were measured by specific and sensitive radioimmunoassays. Duodenal perfusion with HCl and oleate stimulated dose-dependently pancreatic HCO3 and protein secretion and raised plasma levels of secretin and CCK, respectively. Atropine reduced significantly both HCO3 and protein secretion but did not affect plasma secretin and CCK levels in these studies. Both exocrine pancreatic secretion and plasma secretin and CCK levels were suppressed by somatostatin. Meat feeding caused a marked pancreatic HCO3 and protein secretion accompanied by a significant increase in plasma secretin and CCK which seem to play an important role in the postprandial pancreatic stimulation. Both atropine and somatostatin reduced the pancreatic secretion induced by exogenous hormones but only somatostatin, but not atropine, significantly decreased plasma secretin and CCK responses to intestinal stimulants. We conclude that both atropine and somatostatin reduce the pancreatic responses to duodenal HCl or oleate or to meat feeding but only somatostatin is capable of suppressing the release of secretin and CCK.