Responses of the pancreatic digestive enzyme secretion to amino acids, glucose and cholecystokinin in chicks

1. Pancreatic secretion of digestive enzymes, amylase, trypsinogen and chymotrypsinogen, was studied in response to the wing vein injection of digestive end products, various single amino acids and glucose, with or without cholecystokinin (CCK) in chicks. 2. Among amino acids administered, only phenylalanine significantly (P less than 0.05) increased trypsinogen and chymotrypsinogen secretions, while other amino acids did not. 3. Simultaneous injection of single amino acids with CCK increased digestive enzyme secretion to various extents depending on the kind of amino acids whereas the injection of glucose with CCK did not affect when compared with that of CCK alone. 4. By varying doses, a synergetic action of CCK plus amino acid on the secretion of pancreatic digestive enzymes was observed at 0.5 mM for valine and 5 mM for arginine.     

Nonparallel discharge of digestive enzymes from isolated pancreatic acini

The secretion of amylase, trypsinogen, chymotrypsinogen and proelastase from isolated rat dispersed pancreatic acini was investigated in the absence (basal) and presence of two concentrations of CCK8 (50 and 500 pM), carbachol (2.5 and 7.5 microM) and secretin (10 nM and 1 microM). The unstimulated (basal) rate of release of each of the digestive enzymes was essentially the same. However, whereas both doses of CCK8 and carbachol caused a preferential release of chymotrypsinogen over that of amylase and trypsinogen, the magnitude of stimulated release of amylase, trypsinogen and chymotrypsinogen by 1 microM secretin was found to be similar for each of the enzymes. Furthermore, none of the secretagogues caused a significant enhancement in proelastase release. The present data demonstrate that whereas CCK8 and carbachol induce a greater release of chymotrypsinogen over that of amylase or trypsinogen, release of all three enzymes was equally stimulated by secretin from isolated pancreatic acini.     

Caerulein-induced acute pancreatitis in the rat. Pancreatic secretory response to cholecystokinin.

The response of pancreatic exocrine secretion to cholecystokinin (CCK), has been studied in experimental acute pancreatitis induced in rats by supramaximal doses of caerulein. Several doses of caerulein were used (4, 20 and 40 micrograms/Kg) and each one was administered by four subcutaneous injections over 3 h at hourly intervals. Pancreatic juice was collected 9 h after the first injection. The caerulein-treated animals showed a statistically significant increase in serum amylase levels. Secretory activity of ductular cells remained unchanged in all the caerulein-treated animals, but total protein and amylase secretion decreased significantly at all the caerulein doses used, both in resting conditions and under stimulation with CCK (1.25 micrograms/Kg/h). Despite this the acinar cells of rats treated with the lowest dose of caerulein retained a certain degree of secretory function since amylase activity in pancreatic juice was greater than in other groups of rats treated with higher doses of caerulein. Moreover, the percentage of increase observed in total protein and amylase in response to CCK respect to basal secretion is similar to that of the untreated animals. At higher doses (20 and 40 micrograms/Kg) the secretory capacity in response to CCK was inhibited. Therefore CCK administration in slight acute pancreatitis could be used as a therapy since it favours the secretion of pancreatic enzymes at percentual levels similar to those of the controls.     

Effects of combined secretagogues and extracellular calcium on neonatal insulin release

The insulin response of 3-day old neonatal rat islets was evaluated following a 1 h incubation with glucose alone and in the presence of 30 nM sulfated cholecystokinin octapeptide (CCK) and/or 20 microM carbachol (CCh). Insulin secretion was found to be incrementally increased from the lowest glucose concentration and enhanced several fold in the presence of CCK and/or CCh. In combination, CCK and CCh increased glucose-stimulated insulin secretion by an amount equivalent to the sum of their individual increases. The presence of either CCK alone or CCK plus CCh increased phosphoinositide hydrolysis by the same relative amount that they increased insulin secretion when compared to 8.3 mM glucose. Glucose-stimulated insulin secretion was totally inhibited when calcium was omitted from the incubation buffer; this effect was partially negated by CCK alone and more so by CCK combined with CCh. Insulin secretion in response to 8.3 mM glucose alone was unchanged when calcium in the incubation buffer was increased from 1 to 5 mM; however, the insulin response to 16.7 mM glucose alone and 8.3 mM glucose in the presence of CCK and/or CCh was increased under this condition. Thus, we have shown that, even at 3 days postpartum, insulin secretion from isolated islets is a complex response capable of being molded by several secretagogues at once and ultimately determined by interplay of different signaling systems activated.     

Effect of somatostatin on bile-induced acute hemorrhagic pancreatitis in the dog.

In 21 female Beagle dogs an experimental pancreatitis was induced by injection of bile into the pancreatic duct system. Beside controls, dogs received 62.5 micrograms/h cyclic somatostatin (SRIF) a continuous i.v. infusion starting with a bolus of 250 micrograms 15 minutes before or 2 hours after bile injection. Following blood parameters were determined: lipase, amylase, blood count, minerals, glucose, insulin, gastrin, secretin and CCK. Two controls died within 24 hours, the others were sacrificed after 48 hours. All pancreata were examined morephologically. The controls developed all clinical signs of acute hemorrhagic pancreatitis, whereas all SRIF-treated dogs were in much better general condition. Lipase and amylase increased in all groups. In the controls insulin, gastrin and secretin remained unchanged and CCK rose slightly. SRIF-treatment diminished insulin, CCK and the test meal-induced increase of secretin. At autopsy the pancreata of the controls were nearly entirely apoplectic. The SRIF-treated dogs showed less damage of the pancreas and no severe hemorrhagic necrosis was noted. The beneficial effect of SRIF cannot only be due to an interaction with intestinal hormones. An additional direct protective effect on the exocrine parenchyma is proposed to exist.     

Stimulatory role for endogenous opioid peptides on postexercise insulin secretion in rats

Endogenous opioid peptides (EOP) and prior exercise may modulate the stimulatory effect of glucose on insulin secretion. To gain insights into these relationships, we studied male Wistar rats (187-245 g) during sustained hyperglycemia by use of the glucose clamp technique. Four groups of sedentary fed rats (n = 8/group) either ran (Ex) at 24 m/min, 0% grade, or rested (R) for 40 min. Thirty minutes after Ex or R, arterial blood glucose was elevated to and maintained at 11 mM for 2 h by a variable glucose infusion. At the start of Ex or R rats had saline (Sal) or naloxone (Nal, an opioid antagonist) intravenous infusions for 160 min (40 min Ex + 30 min R + 90 min of a 120-min glucose clamp). Steady-state glucose infusion rates (SSGIR) were approximately 55 mg.kg-1.min-1 at the start of the clamp and declined significantly over the 2nd h to approximately 45 mg.kg-1.min-1. No significant differences existed in SSGIR between groups. R-Sal and Ex-Sal groups did not differ in their insulin response to hyperglycemia. In contrast, when all groups were compared at the end of the Nal or Sal infusion, Ex-Nal had the lowest insulin concentration (749 +/- 174 pmol/l), whereas the R-Nal group had the highest (1,581 +/- 216 pmol/l, P less than 0.05). These data suggest a stimulatory role for EOP on insulin secretion that is expressed after a prior stress (Ex). Thus one function of exercise-induced activation of EOP may be to regulate insulin secretion in the immediate postexercise period.     

Hyperglycemic effect of high doses of dobutamine in the rat: studies of insulin and glucagon secretion

The influence of dobutamine on glucoregulation has been assessed in the rat during and after an intravenous infusion given at the following doses: 0, 0.1, 1.0, 10, 100, and 1000 micrograms X kg-1 X min-1. Plasma glucose, insulin, and glucagon levels were measured at 15-min intervals in unanesthetized previously cannulated rats. Basal glucose levels were preserved with the less than or equal to 10 micrograms X kg-1 X min-1 doses. At the greater than or equal to 100 micrograms X kg-1 X min-1 doses, a marked hyperglycemic effect was observed, partly attributable to some inhibitory effect of dobutamine on glucose-induced insulin secretion and to its stimulatory effect on glucagon secretion. Such data suggest that dobutamine may disturb the normal glucose homeostasis, particularly in situations of deficient insulin reserve.     

Effect of aging on the sensitivity of pancreatic beta-cells to insulin secretagogues in rats.

Glucose-stimulated insulin release from rat pancreas is known to be blunted by aging. In the present study, we examined the effect of aging on insulin release induced by various secretagogues using the isolated perfused pancreas of female rats. Insulin release from the perfused pancreas in response to 16.7 mM glucose in 8-month-old rats (older rats) was much less than that in 2-month-old rats (young rats). The first phase of insulin release after glucose stimulation was attenuated in older rats. The addition of 0.1 mM 3-isobutyl-1-methylxanthine (IBMX) potentiated glucose-induced insulin secretion in both groups of rats. However, the second phase of insulin secretion in older rats was lower than that in younger rats. The phorbol ester 12-O-tetradecanoyl phorbol ester (TPA, 200 nM) enhanced both the first and the second phases of insulin release induced by glucose in both groups of rats. The amount of first phase insulin release induced by TPA with glucose in young rats was greater than that in older rats, whereas the second phase of insulin release was similar in both groups of rats. On the other hand, tolbutamide (200 uM) similarly stimulated the first phase of insulin release in both age groups of rat. In addition, the amount of cumulative insulin secretion induced by tolbutamide during the second phase was slightly but significantly greater in older rats than in young controls. Insulin content in the pancreas was significantly greater in older rats than in young rats and increased after the stimulation with TPA and tolbutamide.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of cholecystokinin octapeptide on the pancreatic exocrine secretion in the pig

In conscious pigs, intravenous infusion of serial doses of cholecystokinin octapeptide (CCK8; 2.9-232.3 pmol.kg-1.min-1) upon a background of secretin resulted in a linear increase of plasma CCK-like immunoreactivity (CCK-LI) concentration and evoked a dose-related increase of pancreatic volume and bicarbonate and protein outputs. The threshold plasma CCK-LI concentration for significant pancreatic response was 103.8 +/- 10.2 pM using a CCK8 dose of 8.8 pmol.kg-1.min-1. The maximum pancreatic response was observed for a plasma CCK-LI level of 498.0 +/- 15.3 pM using 77.2 pmol CCK8.kg-1.min-1. In anesthetized pigs, the threshold plasma CCK-LI concentration for pancreatic response was 1500 pM (actual CCK8 dose of 60.3 pmol.kg-1.min-1). The physiological relevance of this finding was assessed by comparing the food-induced increase of pancreatic secretion with that of plasma CCK-LI. Food ingestion was followed by a sharp pancreatic response and by a progressive increase of plasma CCK-LI to a peak increment of about 15 pM. Gel chromatography of portal and peripheral plasma from fed animals revealed three major peaks in the volumes of CCK33/39 and CCK8, and in a volume intermediate between CCK33/39 and CCK8. An additional minor component eluted ahead of CCK33/39. CCK8, which is one of the CCK components released after food intake, appears to be a fairly weak pancreatic stimulant in pigs.     

Nontoxic heat shock protein coinducer BRX-220 protects against acute pancreatitis in rats

Background: Nontoxic heat shock protein (HSP) inducer compounds open up promising therapeutic possibilities by activating one of the natural and highly conserved defense mechanisms of the organism. Aims: In the present experiments, we examined the effects of a HSP coinducer drug-candidate, BRX-220, on the cholecystokinin-octapeptide (CCK)-induced acute pancreatitis in rats. Methods: Male Wistar rats weighing 240 to 270 g were divided into two groups. In group B, 20 mg/kg BRX-220 was administered orally, followed by 75 μg/kg CCK subcutaneously three times, after 1, 3, and 5 h. This whole procedure was repeated for 5 d. The aminals in group B received physiological saline orally instead of BRX-220, but otherwise the protocol was the same as in group B. The rats were exsanguinated through the abdominal aorta 12 h after the last administration of CCK. We determined the serum amylase activity, the plasma trypsinogen activation peptide concentration, the pancreatic weight/body weight ratio, the DNA and total protein contents of the pancreas, the levels of pancreatic HSP60 and HSP72, the activities of pancreatic amylase, lipase, trypsinogen, and free radical scavenger enzymes (superoxide dismutase, catalase, and glutathione peroxidase), the degree of lipid peroxidation, protein oxidation, and the reduced glutathione level. Histopathological investigation of the pancreas was also performed in all cases. Results: Repeated CCK treatment resulted in the typical laboratory and morphological changes of experimentally induced pancreatitis. The pancreatic levels of HSP60 and HSP72 were significantly increased in the animals treated with BRX-220. In group B, the pancreatic total protein content and the amylase and trypsinogen activities were significantly higher vs. group B. The plasma trypsinogen activation peptide concentration, and the pancreatic lipid peroxidation, protein oxidation, and the activity of Cu/Zn-superoxide dismutase were significantly decreased in group B vs. group B, whereas the glutathione peroxidase activity was increased. The morphological damage in group B was significantly lower than that in group B. Conclusion: The HSP coinducer BRX-220, administered for 5 d, has a protective effect against CCK-induced acute pancreatitis.     

Effect of insulin on exocrine pancreatic secretion in healthy and diabetic anaesthetised rats

This investigation characterised the effects of exogenous insulin on exocrine pancreatic secretion in anaesthetised healthy and diabetic rats. Animals were rendered diabetic by a single injection of streptozotocin (STZ, 60 mg kg(-1) I.P.). Age-matched controls were injected citrate buffer. Rats were tested for hyperglycaemia 4 days after STZ injection and 7-8 weeks later when they were used for the experiments. Following anaesthesia (1 g kg(-1) urethane I.P.), laparotomy was performed and the pancreatic duct cannulated for collection of pure pancreatic juice. Basal pancreatic juice flow rate in diabetic rats was significantly (p < 0.001) increased whereas protein and amylase outputs were significantly (p < 0.001) decreased compared to control rats. Insulin (1 IU, I.P.) produced in healthy rats significant increases in pancreatic flow rate, amylase secretion and protein output compared to basal (p < 0.05). Insulin action also included a reduction in blood glucose (152.7 +/- 16.9 mg dl(-1), n = 6, prior to insulin and 42.0 +/- 8.4 mg dl(-1), n = 4, 100 min later). In fact, flow rate and glycaemia showed a strong negative correlation (p < 0.01, Pearson). Pretreatment with atropine (0.2 mg kg(-1), I.V.) abolished the effects of insulin on secretory parameters despite a similar reduction in glycaemia; in this series of experiments the correlation between flow rate and blood glucose was lost. In diabetic rats, insulin (4 IU, I.P.) did not modify exocrine pancreatic secretion. There was a fall in blood glucose (467.6 +/- 14.0 mg dl(-1), n = 10, prior to insulin and 386.6 +/- 43.6 mg dl(-1), n = 7, 120 min later). Rats, however, did not become hypoglycaemic. Similar results were observed in diabetic atropinized rats. The results of this study indicate that the effects of insulin on exocrine pancreatic secretion in anaesthetised healthy rats are mediated by hypoglycaemia-evoked vagal cholinergic activation.     

Amylase secretion from isolated pure acinar cells

Isolation of pure acinar cells of the rat pancreas was achieved employing counterflow sedimentation filtration technique (CSFT). The preparation of purified acinar cells contained an occasional red blood cell (RBC, 200:1) with total absence of endocrine and duct cells. A significant stimulation of amylase secretion from isolated pure acinar cells was produced by octapeptide of cholecystokinin (CCK8) and insulin produced potentiation of the effect of CCK8. Synthetic glucagon inhibited basal and CCK8 stimulated amylase secretion. Non-synthetic purified glucagon stimulated amylase secretion and potentiated the effect of CCK8. Vasoactive intestinal polypeptide (VIP) did not stimulate amylase secretion but potentiated the effect of CCK8. No leakage of lactic dehydrogenase (LDH) was detected from the cells in any of the secretion studies. Thus a highly purified preparation of isolated pure acinar cells of rat pancreas could be obtained with excellent morphologic and functional integrity.     

Biochemical changes in the exocrine pancreas of rats fed caffeine

Coffee consumption has been associated with pancreatic disorders, but the mechanisms involved remain to be elucidated. This investigation examines the effects of caffeine consumption on the structure and function of the exocrine pancreas. Groups of rats, fed ad libitum commercial laboratory diet, were given drinking water which contained either caffeine (0.09 mg/ml) or nothing at all. The rats were allowed drink ad libitum and were killed 6 weeks later. Final body and pancreatic weights were not significantly different between the groups at the end of the experimental period. Although no ultrastructural effects of caffeine on the pancreas were observed, amylase and trypsinogen activity was 35% higher in pancreatic homogenates from caffeine-fed rats compared with controls. In addition, levels of immunoreactive cationic trypsin(ogen) were 41% higher than control levels in pancreases from the caffeine-fed rats. Also, the circulating levels of amylase and immunoreactive cationic trypsin(ogen) in serum were lower in the caffeine group compared with controls. When dispersed pancreatic acini isolated from the caffeine-fed rats were incubated in vitro with increasing concentrations of CCK-8 or nicotine, the rate of release of amylase, trypsinogen, and chymotrypsinogen was lower than in the control rats. This effect did not appear to be due to inhibition of protein synthesis, as determined by [3H]leucine incorporation into acinar protein. These data suggest that prolonged intake of caffeine at common dietary levels inhibits pancreatic enzyme secretion.     

Differential mechanism and site of action of CCK on the pancreatic secretion and growth in rats

Recent studies demonstrated that cholecystokinin (CCK) at physiological levels stimulates pancreatic enzyme secretion via a capsaicin-sensitive afferent vagal pathway. This study examined whether chemical ablation of afferent vagal fibers influences pancreatic growth and secretion in rats. Bilateral subdiaphragmatic vagal trunks were exposed, and capsaicin solution was applied. Pancreatic wet weight and pancreatic secretion and growth in response to endogenous and exogenous CCK were examined 7 days after capsaicin treatment. Perivagal application of capsaicin increased plasma CCK levels and significantly increased pancreatic wet weight compared with those in the control rats. Oral administration of CCK-1 receptor antagonist loxiglumide prevented the increase in pancreatic wet weight after capsaicin treatment. In addition, continuous intraduodenal infusion of trypsin prevented the increase in plasma CCK levels and pancreatic wet weight after capsaicin treatment. There were no significant differences in the expression levels of CCK-1 receptor mRNA and protein in the pancreas in capsaicin-treated and control rats. Intraduodenal administration of camostat or intravenous infusion of CCK-8 stimulated pancreatic secretion in control rats but not in capsaicin-treated rats. In contrast, repeated oral administrations of camostat or intraperitoneal injections of CCK-8 significantly increased pancreatic wet weight in both capsaicin-treated and control rats. Present results suggest that perivagal application of capsaicin stimulates pancreatic growth via an increase in endogenous CCK and that exogenous and endogenous CCK stimulate pancreatic growth not via vagal afferent fibers but directly in rats.     

Effect of pectin on the function of the rat exocrine pancreas

The author studied the effect of three weeks' administration of a 5% pectin concentration in the standard (Larsen) diet on basal and cholecystokinin octapeptide-(CCK8-) stimulated pancreatic exosecretion in rats. Protein, amylase and trypsinogen output determined in pancreatic juice obtained under basal conditions and after CCK8 stimulation of the exocrine pancreas showed no statistically significant differences between rats fed on the standard and the pectin-enriched Larsen diet. Our observations and studies by other authors show that the direct effect of dietary fibre on the exocrine function of the pancreas is an open question as far as further research is concerned.     

Significance of Ca2+, Rb+ fluxes, of cAMP and cGMP for the CCK8-modulated insulin release

In rat pancreatic islets the effects of cholecystokinin-8 (CCK8) on glucose-mediated insulin release, 45Ca2+ net uptake, 45Ca2+ efflux, 86Rb+ efflux, cAMP- and cGMP levels were studied. In the presence of a substimulatory glucose concentration (3 mM) CCK8 concentrations of up to 1 microM had no effect on insulin release, but CCK8 at 10 nM potentiated the stimulatory effect of glucose (11.1 mM). 10 nM CCK8 enhanced glucose-stimulated 45Ca2+ net uptake but was ineffective at substimulatory glucose levels. CCK8 had no effect on cAMP and cGMP levels in the presence of 11.1 mM glucose, CCK8 increased 86Rb+ (a measure of K+) in the presence of both 3 and 11.1 mM glucose. This effect was abolished when Ca2+ was omitted from the perifusion medium. CCK8 did not alter glucose (11.1 mM)-stimulated 45Ca2+ efflux rate. These data indicate that (1) CCK8 potentiates glucose-stimulated insulin secretion possibly via an effect on Ca2+ uptake, 2) by affecting Ca2+ uptake, CCK8 enhances K+ efflux, and 3) CCK8 does not mediate its effect via cAMP or cGMP. With respect to 86Rb+ efflux the mechanism of CCK8 action appears to be different from that of glucose. When the mechanism of CCK action on islets is compared with that on exocrine pancreas (data from others) there are similarities (importance of Ca2+ uptake and non-importance of cAMP and cGMP).     

Cyproheptadine and beta cell function in the rat: insulin secretion from pancreas segments in vitro.

Pancreatic islet cell vacuolization, hyperglycemia, and glucose intolerance develop in rats after oral administration of cyproheptadine (CPH). In order to determine whether these effects were associated with abnormal insulin secretion, pancreas segments from CPH-treated and control rats were compared for their ability to secrete insulin in response to several stimuli. Oral administration of CPH (45 mg/kg/day) to rats for 1 or 8 days inhibited glucose-mediated insulin secretion from pancreas segments obtained 3 and 24 hr after the last dose of the drug. Insulin secretion had returned to normal by 48 hr after drug administration. Intraperitoneal administration of the drug was less effective than oral administration in inhibiting in vitro insulin secretion. Other stimuli for insulin secretion (tolbutamide, glucagon, L-leucine, and dibutyryl 3',5'cyclic AMP), like glucose, were incapable of releasing normal amounts of insulin from pancreas segments of CPH-treated rats. CPH and a metabolite, desmethyl-CPH, inhibited glucose-stimulated insulin secretion when added in vitro to pancreas segments from control rats. This suggests that the inhibition of insulin secretion in pancreas segments taken from animals treated with CPH could be due, at least in part, to the presence of drug and its metabolite in the tissue. A previously observed reduction in the pancreatic content of insulin in CPH-treated rats may also contribute to the abnormal insulin release in animals given the drug.     

Recovery of exocrine pancreas six months following pancreatitis induction with L-arginine in streptozotocin-diabetic rats.

The aim of the present work was to investigate the laboratory and morphologic alterations in the pancreas 6 months after pancreatitis induction with L-arginine (Arg) in normal and streptozotocin (STZ)-diabetic rats. The amylase content of the pancreas was significantly decreased in the Arg-treated groups vs. the control group. No significant changes were observed in the DNA, soluble protein and lipase contents of the pancreas. In the STZ-treated groups, the serum glucose level was significantly elevated, whereas the serum immunoreactive insulin (IRI) level was significantly decreased vs. the control group. In these treated groups, the amylase content of the pancreas was also significantly decreased, but that of trypsinogen was significantly elevated vs. the control group. Histologic sections revealed periductal fibroses, adipose tissue and tubular complexes in the Arg-treated rats, but centroacinar hyperplasia was not observed in these groups. No alterations were observed on histological examination in the diabetic rats vs. normal rats 6 months following pancreatitis induction. In conclusion, a major restitution of the pancreatic enzyme content, but moderate histologic alterations were detected 6 months following pancreatitis induction with Arg. The diabetic state appeared to shift the normal pancreatic enzyme content (decreased amylase and increased trypsinogen) in this long-term study, but not to modify the recovery of the exocrine pancreas 6 months following Arg-induced pancreatitis.     

Exocrine pancreatic secretion: effect of subarachnoidal application of cholecystokinin octapeptide in rats

Administration of cholecystokinin octapeptide (CCK-8) intravenously, or in the subarachnoidal surface of the olfactory lobe in rats, caused an increase in pancreatic protein and amylase secretion. It was observed that for subarachnoidal administration of CCK-8 both protein and amylase outputs were higher than that seen after i.v. injection. This result is consistent with the presence of central CCK receptors which when activated can enhance pancreatic exocrine secretion. The blockade of the effect of CCK by administration of CCK-8-specific antisera proves the specificity of the subarachnoidal CCK-8 stimulation.     

CCK and PYY do not participate in the delayed inhibition of pancreatic secretion, after stimulation by duodenal oleic acid infusion.

The role played by CCK in the stimulation of pancreatic secretion by duodenal infusion of oleic acid in conscious rats was studied using a potent and specific CCK receptor antagonist. CR-1409 did not alter basal secretion, which does not require CCK. The three doses of CR-1409 that were used (2, 4 and 8 mg/kg/h) suppressed the protein response to duodenal infusion of oleic acid and significantly enhanced the delayed inhibition normally observed in control rats (-81%, -87% and -88% vs. -51% of basal in controls). CR-1409 dose-dependently reduced the volume of pancreatic secretion after duodenal infusion of oleic acid (0.40 +/- 0.02, 0.36 +/- 0.02, 0.34 +/- 0.03 vs. 0.48 +/- 0.04 ml/30 min for 2, 4, 8 mg/kg/h and controls, respectively) and revealed a delayed inhibition of volume and a slight reduction of bicarbonate secretion. CCK appears to be directly responsible for the protein and also water response to duodenal infusion of oleic acid, and to be indirectly involved in bicarbonate stimulation. PYY antiserum significantly augmented protein output after duodenal infusion of oleic acid (10.75 +/- 1.40, 14.10 +/- 1.60 vs. 8.60 +/- 1.20 mg/30 min, 1 microliter, 2 microliters and controls), but failed to modify the delayed inhibition: PYY modulates the response to duodenal infusion of oleic acid and is not involved in the delayed inhibition, which was shown to be also present for volume, but which is normally masked by the action of CCK.