The effect of taste on gastric and pancreatic responses in dogs

Six mongrel dogs with gastric and esophageal fistulas (n = 4) or with gastric and pancreatic fistulas (n = 2) were studied to determine the role of taste on gastric and pancreatic secretion. Stimulation of the back of the throat with a range of tastants produced gastric acid, bicarbonate, protein, and pancreatic polypeptide levels that were statistically equivalent to those produced with stimulation of the entire tongue. This suggests that the vagus nerve is the primary mediator of the cephalic phase response to tastants. There were marked individual differences among dogs in the responses to the ten tastants that were tested. On average, monosodium glutamate and seltzer, which mongrel dogs do not normally encounter in their diets, produced lower gastric acid secretion and pancreatic polypeptide release than sweet, sour, salty, bitter, and meaty tastes. The gastric acid secreted by the dogs with esophageal fistulas in response to tastes was only one-half as large as levels previously reported for sight/smell of food and only one sixth as large as those obtained with sham feeding.     

Constructing quality profiles for taste compounds in rats: a novel paradigm

We developed a novel behavioral method, adapted from the work by Morrison (1967), for the assessment of taste quality in rats. Four groups of rats were trained to discriminate a standard stimulus (either NaCl, sucrose, quinine, or citric acid, which are widely thought to represent the four basic human taste qualities of salty, sweet, bitter, and sour, respectively) from the remaining three compounds (each at multiple concentrations). Animals were then tested for generalization to the standard stimuli when test compounds were presented and a quality profile was constructed. Rats generalized novel concentrations of standard stimuli completely to their training concentrations and generalized their responses to mixtures of NaCl and sucrose on the basis of the relative concentrations of the stimulus components. In general, the sugars (at high concentrations), denatonium, tartaric acid, and sodium gluconate generalized to sucrose, quinine, citric acid, and NaCl, respectively. Monosodium glutamate generalized to a mixture of sucrose and NaCl. KCl produced a complex generalization profile with notable quinine and citric acid components. Our procedure supplements the current use of the conditioned taste aversion generalization procedure which has some procedural and interpretive limitations. Although our procedure involves the use of a complex stimulus delivery and response measurement apparatus and requires substantial initial conditioning of animals, once trained, a single cohort of animals can be tested for its response to a substantial number of test stimuli over the course of many months without any ostensible loss of stimulus control.     

Comparison of effects of neurotensin and fat on pancreatic stimulation in dogs

In six conscious dogs with esophageal, gastric, and pancreatic fistulas, the effects of intravenous infusion of neurotensin and intraduodenal instillation of sodium oleate on gastric and pancreatic secretion were determined under basal conditions and after exogenous (secretin and cholecystokinin octapeptides) or endogenous stimulants (feeding and duodenal acidification). Neurotensin given intravenously in graded doses (1.5-200 pmol . kg-1 . min-1) to fasted dogs produced a dose-dependent stimulation of pancreatic bicarbonate and protein secretion reaching, respectively, about 18 and 100% of maximal responses to secretin and cholecystokinin octapeptide (CCK). Duodenal oleate in graded doses (0.5-16 mmol/h) resulted in a similar pattern of bicarbonate and protein secretion but increased plasma neurotensin only to about 10% of that achieved with infusion of exogenous neurotensin producing an equal rate of pancreatic secretion. Neurotensin, like oleate, potentiated the action of secretin and CCK on pancreatic bicarbonate and had additive effects on protein response to these secretagogues. Both neurotensin and oleate increased pancreatic response to liver extract meal kept in the stomach at constant pH (5.5) and the response to sham feeding but decreased the response to ordinary feeding, probably due to the inhibition of gastric acid secretion and reduction of duodenal acidification. Neurotensin given intra-arterially directly to the pancreas or to isolated intestinal segment increased dose dependently the blood flow and oxygen consumption without affecting general circulation. We conclude that 1) neurotensin mimics the pancreatic secretory effects of intestinal fat, 2) neurotensin may contribute in part to fat-induced stimulation of the pancreatic secretion, and 3) the secretory effects of neurotensin are accompanied by a marked stimulation of intestinal and pancreatic circulation and metabolism.     

Influence of enteric parasitism on hormone-regulated pancreatic secretion in dogs.

The objective of this study was to test the hypothesis that enteric parasites affect pancreatic secretion in their host. Pancreatic bicarbonate and protein outputs were studied in dogs with gastric and pancreatic fistulas to determine the secretory response to exogenously administered secretin and cholecystokinin and to intraduodenal stimulation with hydrochloric acid and sodium oleate to release endogenous hormones. Bicarbonate and protein concentrations in pancreatic juice were measured prior to infection with Trichinella spiralis and at various periods during primary and secondary infections. Dose-related increases in secretory activity were observed in uninfected hosts in response to all stimuli. Infected dogs responded like controls to exogenous hormones, but showed reduced secretion under duodenal stimulation during the 1st wk of primary infection. This altered response returned to normal 3 wk after primary infection and did not occur following secondary infection. Results support the conclusion that reduced pancreatic secretion is associated with enteric parasitism and is due to a defect in hormone release or in the supply of hormone available for release.     

Effect of substance P and its C-terminal hexapeptide on gastric and pancreatic secretion in the dog

In five dogs with gastric fistulas, Heidenhain pouches, and pancreatic fistulas, the effects of substance P (SP) and its C-terminal hexapeptide (SP6-11) on gastric acid and pancreatic secretions were determined under basal conditions and in response to secretory stimulation. SP or SP6-11 infused alone in graded doses (0.25-2.0 nmol.kg-1.h-1) caused a slight but significant increase in pancreatic secretions in fasted dogs, but, when given during the secretory stimulation, they caused significant inhibition of these secretions. They reduced gastric acid response to pentagastrin and peptone meal without affecting the serum gastrin level. They caused dose-dependent inhibition of secretin-induced pancreatic bicarbonate secretion and suppressed the pancreatic protein response to caerulein, feeding, and duodenal acidification. SP6-11 was equipotent on a molar basis with SP in the inhibition of gastric or pancreatic secretion, indicating that the C-terminal portion of SP exhibits a full spectrum of the biological action of the intact molecule. The inhibitory effects of SP and SP6-11 on the stomach and pancreas were observed at a dose range that was without any significant influence on the blood pressure, indicating that they are not caused by the interference of the blood flow to the pancreas.     

Quality specific differences in human taste detection thresholds as a function of stimulus volume

Taste detection thresholds for sodium chloride, sucrose, citric acid and quinine sulfate were determined with the Henkin three drop forced-choice method at stimulus volumes 0.05 ml, 0.50 ml, and 0.90 ml, with and without water rinses. Taste thresholds were inversely related to stimulus volume (median rs = -.68 and, within each volume, thresholds did not differ as function of water rinsing. The detection thresholds for sodium chloride (range: 15.06 mM to 6.7 mM), sucrose (range: 24.22 mM to 14.13 mM), citric acid (range: 1.47 mM to 0.5 mM) and quinine sulfate (range: 0.35 mM to 0.12 mM) were similar to those of other investigators using considerably larger stimulus volumes and different psychophysical procedures. The present results demonstrate that the Henkin three drop method provides a more optimal measure of changes in taste sensitivity when stimulus volumes of approximately 1 ml are used in place of the standard 0.05 ml stimulus volume.     

Comparison of vasoactive intestinal peptide and secretin in stimulation of pancreatic secretion.

Pancreatic volume flow as well as bicarbonate and protein secretion have been measured in chronic pancreatic fistula cats and dogs in response to I.V. infusion of VIP and secretin or duodenal perfusion of sodium oleate and HCl solution. 2. VIP and secretin infused I.V. in cats produced superimposable pancreatic dose-response curves for volume flow and bicarbonate secretion, reaching almost identical observed and maximal calculated outputs with both peptides. In dogs, VIP was shown previously to be a much less effective stimulant of pancreatic secretion than secretin and the maximal observed bicarbonate output in response to VIP was only about 17% of that to secretin (Konturek, Thor, Dembinski & Król, 1975). It is condluded that VIP in cats is a secretin-like full agonist, whereas in dogs it is a partial agonist of pancreatic bicarbonate secretion. 3. In cats, secretin and VIP showed equal efficacy and their combination exhibited an augmentatory action on pancreatic bicarbonate secretion with additive kinetics, whereas in dogs, VIP was found to have a lower efficacy than secretin and to inhibit competitively secretin-induced pancreatic secretion. These results might be explained by the interaction of VIP and secretin, two chemically related peptides, on a common receptor site of the exocrine pancreas. 4. Caerulein, an analogue of CCK-PZ, infused I.V. in cats and dogs caused a negligible pancreatic bicarbonate secretion and a potent dose-dependent protein secretion. The combination of graded doses of VIP or secretin with a background dose of caerulein resulted in significantly higher bicarbonate and protein outputs than those induced by VIP or secretin alone. 5. Duodenal perfusion of sodium oleate soap in cats and dogs produced pancreatic dose-response curves for volume flow and bicarbonate output similar to those evoked by VIP in these species. Pancreatic protein secretion in response to luminal oleate was slightly higher than could be accounted for by the action of VIP alone. This might be attributed to the release by oleate not only of endogenous VIP but also CCK-PZ or to the vago-vagal reflexes from gut to pancreas. The results of our combined study on cats and dogs suggest the possibility that oleate releases VIP from the gut and that this peptide may play a physiological role in the stimulation of pancreatic secretion.     

Pancreatic response to intestinal perfusion with lactic acid or acidified albumin.

To test the hypothesis that the permeability of weak acids across the intestinal mucosa affects their ability to stimulate pancreatic bicarbonate output, we compared pancreatic bicarbonate secretion in response to intestinal perfusion with an acid presumed to be permeable to cell membranes, lactic acid (90 daltons), and an acid presumed to be impermeable, acidified bovine serum albumin (about 70,000 daltons). These two substances have similar titration curves from pH 2.00 to pH 4.50. In four conscious dogs with pancreatic fistulas, solutions of these weak acids were perfused at 50 ml/15 min into the intestine at concentrations adjusted to deliver 1, 2, or 4 mmol/15 min of acid titratable to pH 4.50 (threshold pH for bicarbonate stimulation) from an initial pH of 2.00 or 3.50. At both pH 2.00 and 3.50 and at all titratable acid loads, bicarbonate secretory responses to lactic acid and acidified albumin were not significantly different. Equal titratable acid loads of HCl produced much larger secretory responses. The data do not support the hypothesis that permeability of weak acids is a factor, but confirm the observation that weak acids are less potent than strong acids in stimulating pancreatic bicarbonate secretion.     

The Effect of Synthetic Secretin on the External Pancreatic Secretion in Dogs

Henriksen , F. W. The effect of synthetic secretin on the external pancreatic secretion in dogs. Acta physiol. scand. 1968. 72. 433–440. The effect of synthetic secretin on the external pancreatic secretion was investigated in three dogs with Thomas fistulas and gastrostomies. The dose-response curve was determined in two dogs. The maximal secretory capacity equalled that obtained with other secretin preparations. Supramaximal doses of synthetic secretin did not depress the secretion of fluid or bicarbonate. A short-lasting increase in the protein secretion after injection of synthetic secretin is explained as a “wash-out” phenomenon.     

Studies on the inhibition of pancreatic secretion by luminal somatostatin

The effects of somatostatin, instilled into the duodenum or administered intravenously, on pancreatic response to endogenous (meal and duodenal acidification) or exogenous (secretin and caerulein) stimulants were compared in five dogs with gastric and pancreatic fistulas. Somatostatin, whether applied topically to the duodenal mucosa or given intravenously, resulted in qualitatively similar inhibition of pancreatic secretion of water, bicarbonate, and enzyme protein, being about four to eight times less potent after intraduodenal than after intravenous administration. A meal-induced secretion appears to be the most sensitive to the inhibitory action of intraduodenal somatostatin, probably because of the suppression of gastric acid and serum gastrin secretin involved in the postprandial stimulation of the exocrine pancreas. The inhibition of pancreatic secretion by luminal somatostatin was accompanied by a significant increase of plasma levels of the immunoreactive somatostatin, indicating that this peptide can be absorbed intact across the intestinal mucosa. We conclude that somatostatin administered into the gut lumen is absorbed into the circulation and can inhibit pancreatic secretion both by the suppression of the release of gastrointestinal hormones and by direct inhibitory action on the exocrine pancreas.     

Gastric and pancreatic responses to meals varying in pH

1. Gastric acid response to a test meal of 10% peptone was measured in chronic gastric and pancreatic fistula cats using the Fordtran and Walsh method, monitoring the rate at which a solution of 0.5 M sodium bicarbonate had to be added to maintain constant pH of gastric content at pre-selected values ranging from 5.0 to 1.0. Simultaneously, pancreatic secretion was determined by the standard collection technique. In this way the pH profile for the inhibition of gastric secretion and stimulation of pancreatic secretion has been established in cats.2. A peptone meal adjusted to pH 5.0 produced gastric acid output similar to the maximal response to histamine or pentagastrin. It provoked a negligible stimulation of pancreatic flow rate and bicarbonate output but a large protein output.3. Graded decrease of the peptone meal pH to below 4.0 resulted in inhibition of gastric acid production and in a concomitant stimulation of pancreatic secretory volume and bicarbonate output. A meal adjusted to pH 1.0 stimulated gastric secretion only about 30% of the response recorded at pH 5.0. Pancreatic secretion with a meal adjusted to pH 3.0 reached the highest level of about 70% of the maximal response to exogenous secretin.4. Since the observed changes in the secretory activity of the stomach and the pancreas induced by test meals adjusted to pH 3.0 can be fully reproduced by exogenous secretin, it is suggested that in the cat this hormone may be responsible for the gastric inhibitory and pancreatic stimulatory mechanisms activated during normal digestion of food.     

Pancreatic bicarbonate, serum gastrin, and secretin responses to meals varying in pH.

The role of secretin in the postprandial bicarbonate response by the pancreas is not clear. This study reports secretin and bicarbonate secretion after exogenous and endogenous acidification of meal. In dogs with gastric and pancreatic fistulas, a liver extract meal at various pH levels was introduced into the stomach and kept at the preselected pH by intragastric titration. Gastric acid, pancreatic bicarbonate, serum gastrin, and plasma secretin were measured. The meal at pH 7 produced an increase of gastrin levels of 230% above basal and a gastric acid output from a basal of 0.8-16.9 meq/30 min. Acidification of the meal evoked a pH-dependent reduction of gastrin and gastric acid secretion, a pH-dependent elevation of pancreatic bicarbonate, and significant elevation of secretin at pH 3 (43% above basal) and at pH 2 (80% above basal). Postprandial endogenous acidification of a meal, without intragastric titration, also provoked significant release of secretin. Maximal pancreatic bicarbonate secretion in response to exogenous secretin was augmented 30% by the addition of a liver extract meal at pH7. It is concluded that in dogs with pancreatic fistulas, a meal exogenously or endogenously (postprandial) acidified is capable of the release of secretin in immunoassayable amounts. The normal pancreatic bicarbonate response to food may depend partially upon potentiation of the secretin effect by other neurohumoral stimuli.     

Effects of antral distension on pancreatic exocrine secretion in dogs: evidence for a short reflex

In chloralose anesthetized dogs and decerebrated dogs whose pyloric sphincter was submucosally ligated, the pancreatic exocrine secretory response to antral distension was studied. Distensions of the antral pouch with Tyrode's solution and 0.1 N HCl caused graded rises in pancreatic flow and protein and bicarbonate outputs. The serum gastrin concentration gradually rose after the distention with Tyrode's solution, while no rise in serum gastrin was elicited by acid distension. After cervical vagotomy, a reduced pancreatic response persisted but no rise in the serum gastrin was seen. After splanchnicectomy following vagotomy, the pancreatic response became greater than before splanchnicectomy. This pancreatic response was observed even after caeliac and superior mesenteric ganglionectomies, but was completely abolished by an external tight ligature around the pyloric sphincter, or by administration of hexamethonium or atropine sulfate. The results suggest the existence of an antropancreatic short reflex in addition to a long route vago-vagal reflex.     

Taste responses to mixtures: analytic processing of quality

The tastes of 100 mM sodium chloride (NaCl), 100 mM sucrose, and 1 mM quinine hydrochloride in mixtures were investigated in golden hamsters (Mesocricetus auratus) with a conditioned taste aversion (CTA) paradigm. CTAs, established in golden hamsters by injection of lithium chloride, were quantified as percent suppression of control 1-hr stimulus intake. CTAs for 10 of 15 stimulus pairs with common components symmetrically cross-generalized, suggesting that component qualities were recognized in binary and ternary mixtures. However, CTAs to quinine were hardly learned and were weakly expressed when quinine was mixed with NaCl, and generalizations from multiple to single stimuli were stronger than vice versa (i.e., asymmetric). The behaviors reflect peripheral inhibition and/or central mixture suppression. Nonetheless, components retain their distinct qualities in mixtures, suggesting that taste processing is analytic.     

Effects of hunger,satiety and glucose load upon taste intensity and taste hedonics

Subjects rated both the taste intensity and taste pleasantness of 4 compounds representing sweet, salty, sour and bitter, respectively. The typical pleasantness ratings appeared to conform to an inverted L shaped function for sweetness (maximum pleasantness at 1.0 M glucose) and for saltiness, and conformed to a negatively sloping function for citric acid and quinine sulfate. These pleasantness functions appeared robust when testing was performed either after an overnight fast, after breakfast or after lunch, respectively. After a satiating glucose load, however, the pleasantness of glucose taste failed to exhibit a breakpoint at 1.0 M glucose, suggesting that a change occurred in hedonic perception of taste after this exceptionally satiating intake. Satiety seems to influence taste pleasantness, but only to a limited degree, and affects only sweet preferences.     

Interaction between secretin and cholecystokinin-octapeptide in the exocrine rat pancreas in vivo and in vitro.

This study investigates the interaction between physiological doses of the synthetic gut hormones, cholecystokinin-octapeptide (CCK8) and secretin on pancreatic juice secretion in the anaesthetized rat and on amylase secretion and Ca2+ and Mg2+ mobilization in isolated pancreatic segments and acinar cells. CCK8 (150 pmol kg-1 h-1) and secretin (100 pmol kg-1 h-1) evoked marked time course increases in pancreatic juice flow, total protein output and amylase secretion in the anaesthetized rat when administered separately compared to saline controls. Simultaneous intravenous infusion of CCK8 and secretin did not yield either an additive response or a potentiation but instead it caused a decrease in secretory responses. Administration of either polymyxin B (10(-8) mol kg-1 h-1) or staurosporine (10(-8) mol kg-1 h-1), two protein kinase C inhibitors, simultaneously with both CCK8 and secretin caused a further decrease in all secretory parameters. Superfusing pancreatic segments with either CCK8 (10(-11) M) or secretin (10(-11) M) elevated amylase output compared to the smaller response with a combination of CCK8 and secretin. Combining staurosporine (10(-6) M) with CCK8 and secretin resulted in a further decrease in amylase output. CCK8 (10(-11) M) evoked a large increase in radiolabelled Ca2+ influx into pancreatic segments and elevated cytosolic free Ca2+ concentration ([Ca2+]i) in acinar cells loaded with the fluorescent dye, Fura-2. Secretin (10(-11) M) alone had no significant effect on Ca2+ mobilization but it markedly attenuated the increases in radiolabelled Ca2+ influx and [Ca2+]i elicited by CCK8. In superfused pancreatic segments CCK8 (10(-11) M) evoked a net efflux of Mg2+ whereas secretin (10(-11) M) induced a net uptake of Mg2+. Combining secretin with CCK8 also resulted in a net uptake of Mg2+. The results indicate that both Ca2+ and Mg2+ mobilization may be associated with the interaction between CCK8 and secretin in the rat pancreas.     

Pancreatic enzyme response to secretin and cholecystokinin-pancreozymin in the rat

1. The report describes a new technique for collecting pancreatic juice in anaesthetized rats. The technique, which involves perfusion of the duodenum, is particularly suitable for analysing the characteristics of pancreatic enzyme secretion. To ensure stable secretory conditions, the rats were kept at 30 degrees C.2. Different combinations of secretin and cholecystokinin-pancreozymin have been given by continuous intravenous infusion and the patterns of secretion of amylase and trypsin have been defined.3. Maximal secretion of the pancreatic enzymes was observed with 60 IU/kg.hr CCK-PZ (amylase) or 120 CU/kg.hr (trypsin) combined with 0.5 CU/kg.hr (secretin).4. Pancreatic enzyme secretion in response to submaximal stimulation with CCK-PZ was potentiated by secretin.5. Supramaximal stimulation with CCK-PZ resulted in significantly less secretion of pancreatic enzymes than in response to maximal stimulation.6. The pancreatic secretion of enzymes was poorly sustained during constant-rate stimulation with intravenous hormones, at all dose rates.7. The significance and possible mechanisms of the biphasic pattern of enzyme secretion in response to increasing doses of stimulant hormones and the fall-off in enzyme secretion during constant-rate stimulation are discussed.     

Effects of chlorhexidine on human taste perception

Chlorhexidine, a bis-cationic biguanide antiseptic, greatly reduces the perceived intensity of the salty prototype sodium chloride and may prove to be an important probe of mechanisms that underlie the human salty taste quality. Chlorhexidine, which tastes bitter, also reduces quinine hydrochloride taste intensity, but neither sweet sucrose nor sour citric acid is affected. Perceptual intensity rating and quality identification were measured for human subjects before and for 30 min following treatment with 1.34 mM chlorhexidine gluconate. In one experiment, test stimuli were the taste-quality prototypes; in a second experiment, stimuli were series of sodium, halide and sulfate salts. Experiment 1 showed a single 3-min chlorhexidine treatment resulted in reductions in taste intensity that persisted for at least 30 min. Experiment 2 showed a single 2-min chlorhexidine treatment reduced perceptual intensities of halide and sulfate salts except those with divalent cations. Chlorhexidine impaired identification of the salty quality and produced a bitter quality in nonbitter salts and impaired identification of the bitter quality of quinine, but not bitter salts. The specific effect of chlorhexidine on the bitterness of quinine suggests it may bind to the same receptor as quinine. The ability of chlorhexidine to specifically disrupt saltiness of a wide range of salts is consistent with proposed peripheral transduction mechanisms for the salty quality that involve transepithelial ion transport.     

The effect of oral stimulation on human parotid salivary flow rate and alpha-amylase secretion

Unilateral parotid saliva was collected from ten subjects following oral stimulation with water as baseline, and aqueous solutions of starch (2.5, 5.0, and 10%), sucrose (0.1, 0.2, and 0.4 M) sodium chloride (0.075, 0.15, and 0.30 M), and citric acid (0.005, 0.01, and 0.02 M). Salivary flow rate increased with increasing levels of each taste stimulus. At concentrations of equal taste intensity, citric acid evoked the highest flow rate, followed by sodium chloride and sucrose, while starch, in solution, had a minimal effect. Secretion rate patterns for total protein and alpha-amylase mirrored those of flow rate. The total protein and alpha-amylase concentrations of the saliva, and specific activity of alpha-amylase, were influenced by the type but not the concentration of stimulus, with citric acid stimulation resulting in the lowest concentrations and highest specific activity. Sodium ion (Na+) concentration generally increased with increasing stimulated flow rate, while K+, Ca++, and Mg++ concentrations remained relatively constant. Subjects with lower flow rates had a more concentrated saliva than those with high flow, except for Na+ concentration. Oral stimulation resulted in similar changes in protein and alpha-amylase secretion rates for the two groups.     

Effect of bombesin and related peptides on the release and action of intestinal hormones on pancreatic secretion.

1. Pancreatic volume flow as well as bicarbonate and protein secretion from pancreatic fistulas have been measured in response to i.v. infusion of graded doses of bombesin and related peptides containing the COOH-terminal fragment of the bombesin molecule in conscious dogs with intact antrum and in anaesthetized animals with antrectomy, or antrectomy and enterectomy. 2. Bombesin and related peptides given to conscious dogs produced a potent and dose-dependent increase in pancreatic protein output reaching a maximum equal to that induced by the octapeptide of cholecystokinin (OP-CCK) as well as a small rise in bicarbonate output attaining a peak amounting to about 10% of that evoked by secretin. The serum gastrin level rose progressively during the infusion of bombesin to reach a peak with the highest dose of peptide. 3. Bombesin infused i.v. in anaesthetized animals with resected antrum also evoked a marked increase in pancreatic protein secretion without significant changes in the serum gastrin level. Following the removal of the antrum and small intestine, bombesin failed to show any stimulation of the pancreatic secretion or any change in the serum gastrin level. It is concluded that the strong stimulatory action of bombesin and related peptides on pancreatic secretion cannot be entirely ascribed to the release of gastrin but might be attributed at least in part to the release of intestinal hormones, particularly CCK. 4. Atropine and the growth hormone-release inhibiting hormone (GH-RIH), which were shown to inhibit the release of CCK induced by duodenal perfusion of an amino acid mixture, also caused the inhibition of pancreatic protein secretion by bombesin but failed to affect the pancreatic response to OP-CCK. The results indicate that bombesin releases, in addition to gastrin, CCK from the gut by a mechanism largely dependent upon cholingeric innervation.