The influence of intraduodenal administration of pancreatic juice on the bile-induced pancreatic secretion and immunoreactive secretin release in man

The exocrine pancreatic secretion of water, bicarbonate, amylase, and protein and the plasma levels of immunoreactive secretin (IRS) were studied after intraduodenal infusions of bile and pancreatic juice. Pancreatic secretion was obtained by endoscopic cannulation of the main pancreatic duct. Bile and pancreatic juice were infused into the duodenum through separate catheters attached to the outside of the duodenoscope. The unstimulated secretion was collected for 20 min. After intraduodenal stimulation of the pancreatic secretion with a nearly neutral solution of dried cattle bile, juice was collected for another 20-min period. Then, pure pancreatic juice was infused into the duodenum. It was shown that pancreatic juice reduced the flow rate and output of bicarbonate, amylase, and protein significantly (p less than 0.05). A significant reduction in plasma concentration of IRS (p less than 0.05) was also found. In the controls, i.e., when no pancreatic juice was instilled into the duodenum, a further increase in flow rate, bicarbonate secretion, and IRS was found. It is concluded that the exocrine pancreatic secretion and IRS release induced by intraduodenal administration of bile may be depressed by reinfusions of pancreatic juice. The corresponding effect on bicarbonate secretion and IRS release found in this study supports the view that secretin may play an important role in the exocrine pancreatic secretion induced by intraduodenal infusion of bile.     

The Influence of Intraduodenal Administration of Pancreatic Juice on the Bile-Induced Pancreatic Secretion and Immunoreactive Secretin Release in Man

The exocrine pancreatic secretion of water, bicarbonate, amylase, and protein and the plasma levels of immunoreactive secretin (IRS) were studied after intraduodenal infusions of bile and pancreatic juice. Pancreatic secretion was obtained by endoscopic cannulation of the main pancreatic duct. Bile and pancreatic juice were infused into the duodenum through separate catheters attached to the outside of the duodeno-scope. The unstimulated secretion was collected for 20 min. After intraduodenal stimulation of the pancreatic secretion with a nearly neutral solution of dried cattle bile, juice was collected for another 20-min period. Then, pure pancreatic juice was infused into the duodenum. It was shown that pancreatic juice reduced the flow rate and output of bicarbonate, amylase, and protein significantly (p < 0.05). A significant reduction in plasma concentration of IRS (p < 0.05) was also found. In the controls, i.e., when no pancreatic juice was instilled into the duodenum, a further increase in flow rate, bicarbonate secretion, and IRS was found. It is concluded that the exocrine pancreatic secretion and IRS release induced by intraduodenal administration of bile may be depressed by reinfusions of pancreatic juice. The corresponding effect on bicarbonate secretion and IRS release found in this study supports the view that secretin may play an important role in the exocrine pancreatic secretion induced by intraduodenal infusion of bile.     

Inhibition of rat basal pancreatic secretion by intraduodenal bile

The effect on basal exocrine pancreatic secretion of diversion from and reintroduction into the duodenum of bile has been studied on conscious rats provided with pancreatic, biliary and duodenal fistulae. Diversion of bile from the intestine augmented protein output by 30%. After an eight-hour diversion recirculation of bile into the duodenum reduced pancreatic protein output by 30%; volume being not significantly modified. When either bile was diverted or the main bile duct was ligated, a similar inhibition of protein secretion was observed after intraduodenal injections of 20 mM solutions of taurocholate, taurochenodeoxycholate, chenodeoxycholate, and cholate, and of synthetic mixed micelles (bile salts, lecithin). Inhibitory action of bile salts on pancreatic secretion was seen equally whether or not the bile salts were in free or conjugated form or pancreatic juice returned to the intestine. We conclude that unlike man and the dog, bile as well as pancreatic juice inhibits the basal pancreatic exocrine secretion of the rat.     

Influence of bile flow obstruction vs bile diversion on pancreatic secretion in the conscious rat

Changes in pancreatic exocrine functions were compared between conscious rats with bile duct ligation and bile diversion from the duodenum on the first, third, fifth, and seventh postoperative days. Body weight was significantly decreased with time in both groups. Basal secretions of fluid, bicarbonate, and protein remained unchanged throughout the experimental period in bile duct ligated rats, whereas in bile diverted rats, the basal bicarbonate secretion with returning of pancreatic juice to the duodenum increased on the third postoperative day, and the basal protein output significantly increased with time. Basal secretions with returning of pancreatic juice to the duodenum in both groups were higher than that in control (bile and pancreatic juice returned to the intestine) rats. Stepwise increases in fluid and bicarbonate outputs responding to the graded doses of secretin were observed in bile duct ligated rats on the first and third postoperative days, as has been observed in bile diverted rats. However, on the fifth and seventh postoperative days, stepwise responses to graded doses of secretin were no longer observed in bile duct ligated rats. The pancreatic response to cerulein was greater in bile diverted rats than in bile duct ligated rats. Plasma CCK concentration in 7-d bile duct ligated rats (4.7 pM) was significantly higher than that in 7-d bile diverted rats (1.6 pM), although the pancreatic wet weight, protein concentration, and total content were comparable for the two groups. It was suggested that the presence of bile in the duodenum is required to maintain normal pancreatic secretion, and that the removal of bile from the intestine has quite different effects, depending on whether the bile flow is obstructed or diverted.     

Influence of bile flow obstruction vs bile diversion on pancreatic secretion in the conscious rat

Changes in pancreatic exocrine functions were compared between conscious rats with bile duct ligation and bile diversion from the duodenum on the first, third, fifth, and seventh postoperative days. Body weight was significantly decreased with time in both groups. Basal secretions of fluid, bicarbonate, and protein remained unchanged throughout the experimental period in bile duct ligated rats, whereas in bile diverted rats, the basal bicarbonate secretion with returning of pancreatic juice to the duodenum increased on the third postoperative day, and the basal protein output significantly increased with time. Basal secretions with returning of pancreatic juice to the duodenum in both groups were higher than that in control (bile and pancreatic juice returned to the intestine) rats. Stepwise increases in fluid and bicarbonate outputs responding to the graded doses of secretin were observed in bile duct ligated rats on the first and third postoperative days, as has been observed in bile diverted rats. However, on the fifth and seventh postoperative days, stepwise responses to graded doses of secretin were no longer observed in bile duct ligated rats. The pancreatic response to cerulein was greater in bile diverted rats than in bile duct ligated rats. Plasma CCK concentration in 7-d bile duct ligated rats (4.7 pM) was significantly higher than that in 7-d bile diverted rats (1.6 pM), although the pancreatic wet weight, protein concentration, and total content were comparable for the two groups. It was suggested that the presence of bile in the duodenum is required to maintain normal pancreatic secretion, and that the removal of bile from the intestine has quite different effects, depending on whether the bile flow is obstructed or diverted.     

Relative Importance of Pancreatic,Hepatic, and Mucosal Bicarbonate in Duodenal Neutralization of Acid in Anaesthetized Pigs

Pancreatic and hepatic bicarbonate secretion and the disappearance rate of acid during duodenal acidification were measured simultaneously in anaesthetized pigs. Perfusion of the duodenum with HCI resulted in an increase in both hepatic and pancreatic bicarbonate secretion. During all acid loads hepatic bicarbonate secretion was significantly greater than pancreatic secretion. Furthermore, the disappearance rate of acid in the duodenum during diversion of both bile and pancreatic juice was significantly greater than the amount of acid which could be neutralized by the concomitant pancreatic bicarbonate secretion. Diversion of pancreatic juice from the duodenum did not affect the disappearance rate of acid at any acid load, whereas diversion of bile caused a significant decrease. Thus, in the anaesthetized pig the liver and the duodenal mucosa are of greater importance than the pancreas for the neutralization of acid in the duodenum. It is suggested that the importance of the pancreatic contribution to duodenal neutralization should be reevaluated in other species, including man.     

Relative importance of pancreatic, hepatic, and mucosal bicarbonate in duodenal neutralization of acid in anaesthetized pigs.

Pancreatic and hepatic bicarbonate secretion and the disappearance rate of acid during duodenal acidification were measured simultaneously in anaesthetized pigs. Perfusion of the duodenum with HCl resulted in an increase in both hepatic and pancreatic bicarbonate secretion. During all acid loads hepatic bicarbonate secretion was significantly greater than pancreatic secretion. Furthermore, the disappearance rate of acid in the duodenum during diversion of both bile and pancreatic juice was significantly greater than the amount of acid which could be neutralized by the concomitant pancreatic bicarbonate secretion. Diversion of pancreatic juice from the duodenum did not affect the disappearance rate of acid at any acid load, whereas diversion of bile caused a significant decrease. Thus, in the anaesthetized pig the liver and the duodenal mucosa are of greater importance than the pancreas for the neutralization of acid in the duodenum. It is suggested that the importance of the pancreatic contribution to duodenal neutralization should be reevaluated in other species, including man.     

Aging and pancreatic exocrine function: studies in conscious male rats

Changes in pancreatic exocrine function in young (6- and 12-month-old) and old (24- to 27-month-old) male Fischer (F-344) rats were examined. Rats were prepared with cannulae draining bile and pancreatic juice separately and with duodenal and right jugular vein cannulae. Experiments were conducted between the third and the seventh postoperative day in conscious rats. Bile and pancreatic juice were returned to the intestine during both the recovery period and between experiments. Pancreatic responses to endogenous [bile-pancreatic juice (BPJ) diversion from the intestine] and exogenous stimulation [0.086, 0.432, and 1.728 nmol/kg secretin and 0.033, 0.167, and 0.667 nmol/kg cholecystokinin-octapeptide (CCK-8)] were determined. Basal secretions of fluid, bicarbonate, and protein were not affected by aging. The pancreatic responses of fluid and bicarbonate secretion to BPJ diversion or secretin were unaffected by aging. However, the increment of protein secretion in response to BPJ diversion and the largest dose of CCK-8 was attenuated in old rats. It appears the duct cell function is hardly affected by aging, but that the reserve capacity for protein secretion in response to stimulation may decrease in old rats.     

Effect of taurocholate on CCK release and pancreatic secretion produced by two CCK-releasing peptides in conscious rats.

The role of luminal bile salts (taurocholate) in regulation of rat pancreatic secretion was examined by studies on the effects of luminal stimulants on the pancreas during infusion of various concentrations of taurocholate into the duodenum of conscious rats. Rats with external bile and pancreatic fistulae were used. For 24 h before the experiment, pancreatic juice was excluded from the intestine but bile was continuously returned to the duodenum. From the beginning of the experiment, 8-200 mM of taurocholate was infused at a rate of 1 ml/h instead of returning the bile. Pancreatic juice was collected for a 2-h period and then 2 micrograms of pancreatic secretory trypsin inhibitor-61 (PSTI-61) (= monitor peptide) or partially purified putative CCK-releasing peptide from rat intestine (intestinal CCK-RP) was injected into the duodenum (1 ml/min). Continuous infusion of taurocholate maintained a constant rate of pancreatic secretion, except at a concentration of 8 mM, which resulted in a slight increase in pancreatic secretion. Both PSTI-61 and intestinal CCK-RP significantly increased pancreatic secretions during infusion of 20 or 40 mM taurocholate, but had no significant effect during infusion of 80 or 200 mM taurocholate. Therefore, higher concentrations of taurocholate in the intestine prevented the stimulatory effects of luminal stimulants, probably by preventing the latter from reaching CCK cells.     

The unstimulated pancreatic secretion obtained by endoscopic cannulation, and the plasma secretin levels in man.

The technique of collecting juice from the main pancreatic duct by siphonage is described. The juice was collected in 5-min fractions under basal conditions for 20 min (32 subjects) and extended to 60 min (6 subjects). Flow rate and bicarbonate concentration were significantly higher during the first collected samples, whereas concentrations of amylase and protein rose during the first 20 min of the study. All variables remained nearly constant after this period. Immunoreactive secretin (IRS) in peripheral plasma was significantly higher immediately after cannulation of the main pancreatic duct, as compared to the pre-endoscopic level. When the catheter was left in the duct and pancreatic juice drained, the IRS stabilized at a level not significantly different from the pre-endoscopic level. Positive correlations were found between flow rate and plasma level of IRS and between flow rate and bicarbonate concentrations. A negative correlation was found between the flow rate and concentrations of amylase and protein. The higher flow rate, plasma level of IRS, and bicarbonate concentration at the beginning of the examination may be due to the presence of acid and/or bile in the duodenal contents shortly after the endoscope enters the duodenum. Later in the procedure the levels have stabilized, which indicates that little or no acid or bile is passing into the duodenum. It is also concluded that secretin may be one factor responsible for the basal pancreatic secretion in man.     

Pancreatic, hepatic, and duodenal mucosal bicarbonate secretion during infusion of secretin and cholecystokinin. Evidence of the importance of hepatic bicarbonate in the neutralization of acid in the duodenum of anaesthetized pigs

The effect of infusion of secretin alone or in combination with cholecystokinin (CCK) on pancreatic, hepatic, and duodenal mucosal bicarbonate secretion was studied in anaesthetized pigs. After laparotomy, catheters were inserted into the common bile duct, the pancreatic duct, and both ends of the duodenum. Pancreatic, hepatic, and duodenal mucosal secretions were collected during intraportal infusion of increasing doses of secretin, either alone or in combination with CCK. During infusion of secretin in doses that caused physiologic increases in plasma secretin concentrations the liver produced significantly more bicarbonate than the pancreas. A physiologic dose of CCK augmented the effect of secretin on both hepatic and pancreatic bicarbonate secretion, but the hepatic production of bicarbonate was still larger than the pancreatic production. Neither secretin alone nor secretin combined with CCK caused any changes in duodenal mucosal bicarbonate secretion. These results suggest that the liver plays an important role in the neutralization of acid in the duodenum.     

Pancreatic,Hepatic, and Duodenal Mucosal Bicarbonate Secretion during Infusion of Secretin and Cholecystokinin: Evidence of the Importance of Hepatic Bicarbonate in the Neutralization of Acid in the Duodenum of Anaesthetized Pigs

The effect of infusion of secretin alone or in combination with cholecystokinin (CCK) on pancreatic, hepatic, and duodenal mucosal bicarbonate secretion was studied in anaesthetized pigs. After laparotomy, catheters were inserted into the common bile duct, the pancreatic duct, and both ends of the duodenum. Pancreatic, hepatic, and duodenal mucosal secretions were collected during intraportal infusion of increasing doses of secretin, either alone or in combination with CCK. During infusion of secretin in doses that caused physiologic increases in plasma secretin concentrations the liver produced significantly more bicarbonate than the pancreas. A physiologic dose of CCK augmented the effect of secretin on both hepatic and pancreatic bicarbonate secretion, but the hepatic production of bicarbonate was still larger than the pancreatic production. Neither secretin alone nor secretin combined with CCK caused any changes in duodenal mucosal bicarbonate secretion. These results suggest that the liver plays an important role in the neutralization of acid in the duodenum.     

Duodenal output of lactoferrin in normal subjects and correlation to output of amylase, bicarbonate, and total bile acids

Nineteen normal subjects were studied before and after pancreatic stimulation. Duodenal flow was quantitated by means of a dilution indicator technique, and the secretion pattern of lactoferrin, amylase, total bile acids, and bicarbonate was studied. Output of lactoferrin in the duodenum was increased both after stimulation with a test meal and after hormonal stimulation by cholecystokinin alone or cholecystokinin in combination with secretin. Output of lactoferrin was not affected by stimulation by secretin alone. Lactoferrin was secreted in parallel with amylase and bile acids. The results indicate that the origin of lactoferrin in duodenum can be bile or pancreatic juice, or a combination of these.     

Effect of intravenous lipid on human pancreatic secretion

Parenteral alimentation, including intravenous fat, is sometimes used in the treatment of patients with pancreatitis, although the effect of intravenous fat on human pancreatic secretion has not been systematically studied. Intravenous fat, however, has been shown to stimulate pancreatic protein secretion in the dog. The purpose of these studies was to clarify the effect of intravenous fat on human pancreatic secretion. Pancreatic secretion was assessed by measurement of enzymes and bicarbonate in duodenal aspirate collected via a double-lumen tube from 6 healthy volunteers. Four studies were randomly conducted on different days. On day 1, graded concentrations of Intralipid (5%, 10%, and 20%) were given intravenously for 1 h each, while secretin (8.2 pmol . kg-1 . h-1) was given as a background. On day 2, the same doses of Intralipid were infused intravenously without secretin. On day 3, the same doses of Intralipid were perfused into the intestine, and, finally, on day 4, 20% Intralipid was given by intestinal infusion for 2 h while 10% Intralipid was infused intravenously during the second hour. Significant stimulation of enzyme secretion was observed only during the infusion of fat into the intestine, not after intravenous infusion at any concentration. Pancreatic enzyme secretion, stimulated by intraintestinal fat, was not significantly modified by simultaneous intravenous lipid infusion. We conclude that since intravenous fat does not stimulate pancreatic secretion, its use in conditions where pancreatic stimulation is undesirable appears safe.     

Effect of intraluminal bile on the feedback regulatory mechanism of pancreatic enzyme secretion in conscious rats

The effect of intraluminal bile on the well-known feedback regulatory mechanism of exocrine pancreatic secretion exerted by intraluminal trypsin was investigated in conscious rats with pancreatic, biliary and duodenal fistulae. The stimulated pancreatic enzyme secretion caused by diversion of bile-pancreatic juice from the intestine was apparently suppressed by intraduodenal reintroduction of pancreatic juice or bile-pancreatic juice, while it was slightly suppressed by intraduodenal reintroduction of bile. Although additional reintroduction of bile did not alter the already suppressed pancreatic enzyme secretion by the presence of pancreatic juice in the intestine, diversion of bile stimulated the suppressed pancreatic enzyme secretion by intraluminal bile-pancreatic juice. Infusion of sodium taurocholate into the duodenum with diversion of bile-pancreatic juice effectively inhibited pancreatic enzyme secretion. The inhibitory effect seemed to be dependent on the concentration of taurocholate infused into the duodenum. The results suggest that bile and bile acid have an important role in the feedback regulatory mechanism of pancreatic enzyme secretion, at least partly directly inhibiting the secretion.     

Pancreatic bicarbonate response to food-bound hydrogen ion along the gut

Recent reports suggest most solid food enters the duodenum as small particles. Our studies showed that small particles of liver were capable of binding hydrogen ions (H+), but there was slow equilibration of H+ between particulate and aqueous phases. We wondered whether titratable acid as H+ bound to meat particles could effectively stimulate pancreatic bicarbonate secretion despite slow diffusion. We studied mongrel dogs with chronic pancreatic fistulas; the intestinal lumen was washed free of endogenous pancreatic enzymes. Pancreatic bicarbonate and protein responses were measured during duodenal perfusion with pH 2 or pH 3 gels that delivered 1, 2, or 4 mEq/15 min of titratable acid (endpoint pH 4.5). Gels consisted of acidified, 0.1-0.7-mm particles of beef liver or bovine serum albumin or lactic acid suspended with 2% starch in 0.15 M NaCl. The liver, bovine serum albumin, and lactate had similar titration curves. At pH 2 or pH 3, liver particles were about as effective as bovine serum albumin in stimulating pancreatic bicarbonate secretion. Likewise, pH 3 liver particles were equipotent with pH 3 lactate on pancreatic bicarbonate secretion when both perfusates were allowed access to the whole intestine. However, when confined to the first 45 cm of proximal intestine, much less H+ was dissipated from the liver versus the lactate; and, correspondingly, there was a much greater decrement in pancreatic bicarbonate secretion from whole gut responses with liver versus lactate. We conclude that titratable acid bound to solid food particles is a potent stimulus of pancreatic bicarbonate secretion despite its slow diffusion. Our studies suggest that H+ slowly diffusing from particles excites pancreatic bicarbonate secretion by triggering H+ receptors along more distal intestine.     

Luminal bile regulates cholecystokinin release in conscious rats

The effects of intraluminal bile on cholecystokinin release and pancreatic exocrine secretion were studied in conscious rats. Since it has been suggested that bile acid may influence pancreatic secretion indirectly by interacting with luminal protease activities, intraduodenal protease activities were eliminated by pancreatic juice diversion accompanied with simultaneous intraduodenal infusion of aprotinin. This treatment resulted in gradual increases in pancreatic juice flow, bicarbonate and protein outputs, and an increase in plasma cholecystokinin levels, reaching plateau levels 2 hr after the start of the treatment. When endogenous bile was excluded from the intestine, the pancreatic secretion and plasma cholecystokinin concentrations further increased. The intraduodenal infusion of sodium taurocholate during bile pancreatic juice diversion inhibited cholecystokinin release, while pancreatic protein output was only transiently decreased. The results indicate that bile in the duodenum directly regulates cholecystokinin release, probably through its major components, bile salts.     

Modulation of external pancreatic secretion by endogenous norepinephrine: study with a norepinephrine uptake blocker in the rat

The effect of endogenous catecholamines on pancreatic secretion was analyzed with nisoxetine, a specific norepinephrine uptake blocker, and specific adrenoceptor antagonists in anesthetized acute fistula rats. Nisoxetine was administered alone or with alpha-1 (prazosin), alpha-2 (idazoxan or yohimbine), or beta (propranolol) adrenoceptor antagonists. Pancreatic secretion was measured in basal conditions or after stimulation by 2-deoxy-D-glucose (2DG), electrical vagal stimulation, or acetylcholine. (a) Basal. Nisoxetine alone had no effect. Associated with idazoxan or yohimbine, nisoxetine produced a dose-related stimulation (p < 0.01) of water and electrolyte without changing protein output. Addition of propranolol abolished this stimulation. (b) 2DG. Nisoxetine inhibited 2DG-induced secretion (p < 0.01). Idazoxan or yohimbine suppressed the nisoxetine inhibition of water and electrolyte output (p < 0.01) but had no effect on protein output, which was restored only by adding a mixture of idazoxan, prazosin, and propranolol. (c) Electrical stimulation. Nisoxetine did not modify water and electrolyte but inhibited protein response by 75%. Adding idazoxan to nisoxetine significantly increased (p < 0.01) water and bicarbonate response and partly restored protein response. Water and bicarbonate response was restored by propranolol, whereas protein response was only restored by adding a mixture of idazoxan, prazosin, and propranolol. (d) Nisoxetine did not modify pancreatic response to acetylcholine. In conclusion, endogenous norepinephrine affects the response to vagally mediated effects through several subtypes of adrenoceptors, without changing basal or acetylcholine stimulated secretion.     

Stimulatory and inhibitory effects of bile salts on rat pancreatic secretion.

The effects of various species of bile salts (chenodeoxycholate, deoxycholate, ursodeoxycholate and cholate, and their taurine and glycine conjugates) on pancreatic exocrine secretion were studied in conscious rats with external bile and pancreatic fistulae. For examination of the stimulatory effects of bile salts, bile and pancreatic juice were collected for a basal period of 90 minutes and returned to the intestine, and then solutions of bile salts (60 mmol/L) were infused intraduodenally at a rate of 1 mL/h for 2 hours. For examination of their inhibitory effects, pancreatic secretion was stimulated by exclusion of the bile and pancreatic juice; and then solutions of the bile salts were again infused intraduodenally. Chenodeoxycholate, glycochenodeoxycholate, ursodeoxycholate, deoxycholate, and its conjugates (glycodeoxycholate and taurodeoxycholate) significantly increased the fluid, bicarbonate and protein outputs, and bicarbonate concentration, with decrease in protein concentration. These increases were partially inhibited by infusion of either a cholecystokinin antagonist or secretin antibody. In contrast, cholate, taurocholate, tauroursodeoxycholate, glycoursodeoxycholate, and taurochenodeoxycholate inhibited pancreatic secretion and increase in the plasma cholecystokinin concentration produced by exclusion of bile and pancreatic juice. Thus, some bile salts, including taurocholate and taurochenodeoxycholate (major bile salts in rat bile) inhibited pancreatic secretion and cholecystokinin release, whereas some other bile salts increased pancreatic secretion via cholecystokinin release and secretin release.     

Role of secretin in basal and fat-stimulated pancreatic secretion in conscious rats

The role of endogenous secretin in basal and fat-stimulated pancreatic exocrine secretion was investigated in conscious rats. Rats were prepared with chronic fistulas draining bile and pancreatic juice, which was collected and returned to the duodenum at all times. Six days postoperative rats were fasted overnight, and pancreatic protein and fluid secretion were monitored for 3 h under basal conditions (0.15 M NaCl, intraduodenally) and during 2 h of intraduodenal infusion of a 20% triglyceride emulsion (Liposyn). Solutions were infused at 4.6 ml/h. Rats received a single bolus injection of 0.1 ml antisecretin serum or normal rabbit serum starting in the second hour of the basal period, and the effect on basal and fat-stimulated pancreatic protein and fluid secretion was determined. Antisecretin serum significantly inhibited basal interdigestive pancreatic protein and fluid secretion by 43% and 36%, respectively. Infusion of 20% fat emulsion stimulated a 2.1-fold increase in pancreatic protein and fluid secretion. The stimulation of both protein and fluid secretion was significantly inhibited by 60% by antisecretin serum. Plasma secretin after 2 h of fat infusion was 17.7 +/- 1.8 pM and was greatly reduced by the presence of secretin antiserum. The results support the hypothesis that secretin released by fatty acids is an important mediator of the pancreatic protein and fluid secretory response to dietary fat in the rat.