Direct,concentration-dependent inhibition by taurocholate of pancreatic exocrine secretion and CCK release in conscious rats

In conscious rats, bile inhibits pancreatic secretion. The role of luminal taurocholate (TC), a major component of rat bile, in the regulation of pancreatic secretion was studied in conscious rats with external bile and pancreatic fistulae. On the fourth postoperative day, after the basal collection of bile and pancreatic juice (PJ) returned to the duodenum, graded doses of TC (0, 0.4, 4, 40 mM) containing 10 mM CaCl₂ were infused into the duodenum instead of bile and PJ for 2 hr (1 ml/hr), with or without 1 mg/ml of porcine trypsin. Luminal trypsin activities were not affected by any dose of TC. The increases in pancreatic secretion in response to diversion of bile and PJ were progressively inhibited with increasing doses of infused TC from 0 mM to 4 mM both with and without trypsin infusion. The effects with 4 and 40 mM TC were not significantly different. Changes in plasma cholecystokinin concentrations roughly correlated with changes in protein output in rats without trypsin infusion. We concluded that TC directly inhibited pancreatic secretion independent of the luminal trypsin activity and that its inhibitory action was concentration dependent.     

Dissociation of cholecystokinin and pancreaticobiliary response to intraduodenal bile acids and cholestyramine in humans

The role of intraduodenal bile acids in the regulation of cholecystokinin (CCK), pancreatic polypeptide (PP), and secretin as well as exocrine pancreatic and biliary secretion was investigated by means of a duodenal marker perfusion technique in volunteers. The following solutions were perfused: (1) liquid test meal, (2) test meal with 6 g cholestyramine, (3) test meal with 2 g chenodeoxycholic acid (CDC), (4) test meal with 6 g cholestyramine and 2 g CDC, (5) 6 g cholestyramine alone, and (6) 2 g CDC alone. The test meal caused an immediate increase in CCK and PP plasma levels, whereas secretin was not significantly altered. CCK release was further enhanced by addition of cholestyramine, whereas CDC inhibited release. The stimulatory effect of cholestyramine was abolished by CDC. CDC alone and in combination with the test meal stimulated secretin release. The response of PP to the test meal was not altered by addition of either compound. Cholestyramine and CDC alone caused only a very small increase in CCK levels, whereas PP was stimulated to nearly postprandial values. Meal-stimulated pancreatic and biliary secretion was significantly enhanced by cholestyramine, CDC, and the combination of both. CDC and cholestyramine alone each stimulated enzyme and bile secretion to a greater extent than the test meal. We conclude that intraduodenal bile salts are a modulator of postprandial CCK release. Changes in exocrine pancreatic and biliary and PP secretion do not necessarily parallel CCK concentrations, suggesting that different mediators are involved in the observed bile acid-induced changes in humans.     

Role of secretin and cholecystokinin in oleic acid-stimulated pancreatic secretion in rats

We investigated the possible role of endogenous secretin and cholecytokinin (CCK) on oleic acid-stimulated pancreatic exocrine secretion in anesthetized rats. Intraduodenal infusion of oleic acid (pH 6.5) in three different doses (0.06, 0.25 and 1 mmole/hr) resulted in dose-related increases in pancreatic juice volume, bicarbonate and amylase outputs (r=0.665, 0.736 and 0.517, respectively) (P<0.001). Plasma secretin and CCK concentrations also elevated significantly in response to oleic acid, in a dose-related manner (r=0.721 and 0.546, respectively) (P<0.001). There were statistically significant correlations between plasma secretin concentrations and bicarbonate outputs, and between plasma CCK concentrations and amylase outputs in response to oleic acid (P<0.01). Potent CCK antagonist, CR 1409 (5 mg/kg.hr) administered intravenously suppressed completely increase in amylase output induced by oleic acid, and partially in juice volume and bicarbonate output. It is concluded that both endogenous secretin and CCK play important roles on oleic acid-induced pancreatic secretion in rats. The results of this study were presented at The 7th International Symposium of Gastrointestinal Hormones in Shizuoka, Japan, Nov. 1–4, 1988, and appeared in abstract form in Biomedical Research 1988;9(Suppl. 1):114. This work was supported in part by grants from the Japanese Ministry of Education and the Ministry of Welfare. The authors are grateful to Y. Hirasawa, B.S. and M. Takeda, B.S. for their technical assitance.     

Role of endogenous bile on basal and postprandial CCK release in humans

The role of intraduodenal bile in regulation of plasma cholecystokinin (CCK) levels were investigated in patients with obstructive jaundice under external bile diversion and under physiological bile flow into the duodenum by internal bile drainage. Basal plasma CCK levels determined by a specific and sensitive bioassay in patients under external bile drainage (2.2±0.2 pmol/liter; mean±se) were significantly higher than those in control subjects (1.0±0.3 pmol/liter). In control subjects, the peak CCK response (6.2±0.7 pmol/liter) to a test meal was seen at 45 min, whereas that in patients under external bile drainage, it was seen at 20 min after a test meal (17.6±3.2 pmol/liter;P<0.01 vs controls). After peak response, plasma CCK levels in controls gradually decreased, but remained significantly elevated during a 3-hr observation period. In patients under bile diversion, the test meal caused a prompt plasma CCK peak, with a transient fall followed by a continuous rise until 180 min postprandially. In six patients, external bile diversion was changed to internal biliary drainage with a stent tube within two weeks to maintain physiological bile flow into the duodenum. Internal bile drainage normalized basal (0.9±0.2 pmol/liter) as well as meal-stimulated CCK release (peak value: 5.0±0.8 pmol/liter). These results demonstrate that endogenous bile exerts tonic inhibition on basal and postprandial plasma CCK levels in humans.Supported in part by a grant from the Japanese Ministry of Health and Welfare (Intractable Diseases of the Pancreas).     

Duodenum preservation in pancreatic head resection to maintain pancreatic exocrine function (determined by pancreatic function diagnostant test and cholecystokinin secretion)

Background/Purpose

Organ-preserving surgery, such as pylorus-preserving pancreatoduodenectomy (PPPD), duodenum-preserving pancreatic head resection (DPPHR), or medial pancreatectomy (MP), is one of the recent advances in pancreatic surgery. There was a previous report that preservation of the duodenum maintained pancreatic function. However, concerning the resected pancreas, patients were divided into two groups; one group included pancreatic head resections such as Whipple, PPPD, and complete DPPHR, and the other group included MP that removed only the pancreatic neck and preserved the pancreatic head and distal pancreas. The present study was designed to clarify the significance of duodenum preservation, in comparison with duodenum removal, in patients with pancreatic head resection, in terms of pancreatic function, determined by a pancreatic function diagnostant (PFD) test and cholecystokinin (CCK) secretion.

Methods

The subjects were 61 patients (10 with Whipple, 41 with PPPD, and 10 with complete DPPHR). PFD tests and postprandial plasma CCK secretion were used for evaluation.

Results

There was a significant difference between pre- and postoperative PFD values in the patients who received Whipple or PPPD; however, there was no difference in those who had complete DPPHR. Concerning the postoperative PFD value, complete DPPHR was superior to Whipple and PPPD. Regarding postprandial CCK secretion, the pre- and postoperative values were significantly different in the patients with Whipple or PPPD, but there was no difference in those with complete DPPHR. Comparing the three kinds of operations, complete DPPHR was superior to the other two procedures in its maintenance of pancreatic function. There was the significant correlation between CCK and PFD in our patients in the Spearman Rank Correlation (P < 0.0029) and Fisher’s r to z (P < 0.0058).

Conclusions

When pre- and postoperative pancreatic exocrine function and postprandial CCK secretion were measured in patients with pancreatic head resection, it was found that preservation of the entire duodenum was an important factor for maintaining pancreatic function.     

Effect of natural peptide YY on pancreatic secretion and cholecystokinin release in conscious dogs

The effects of natural peptide YY on pancreatic secretion under different stimulatory conditions and on fatty acid-induced cholecystokinin release were examined in five conscious dogs with pancreatic and gastric fistulas. Intravenous infusion of natural peptide YY at 1 and 0.2 g/kg/hr caused 60 and 40% inhibition of secretin- and cholecystokinin-stimulated secretion, respectively, and 40–50 and 20–40% inhibition of intraduodenal oleate stimulated secretion, respectively. A significant but transient decrease in the plasma cholecystokinin level was observed in response to peptide YY under oleate stimulation. The present study demonstrates that peptide YY has a potent inhibitory effect on both exogenously and endogenously stimulated pancreatic secretion and has a mild suppressive effect on fatty acid-induced cholecystokinin release, suggesting that this peptide is an important colonic inhibitor of pancreatic secretion.This work was supported in part by a grant from the Ministry of Education, Japan (A 59440057) and in part by NIH grant AM30415.     

Impaired pancreatic exocrine function in rats with carbon tetrachloride-induced liver cirrhosis

Summary Background Substantial numbers of studies have revealed the close correlation between chronic pancreatitis and cirrhosis in human. However, the situation with regard to pancreatic enzyme secretion is less clear. Aim The aim of the study was to investigate pancreatic exocrine function in rat with carbon tetrachloride-induced liver cirrhosis in rats. Methods Pancreatic exocrine function and morphology in Sprague-Dawley rats with carbon tetrachloride-induced liver cirrhosis were investigated. Pancreatic exocrine functions stimulated by cholecystokinin-8 and other secretagogs were assessed in isolated pancratic acini, and in vivo and morphological changes were studied by routine were assessed in isolated pancreatic acini, and in vivo and morphological changes were studied by routine histological examination and electron microscopy. Results The basal and cholecystokinin-8-stimulated amylase releases from acini and acinar amylase content were significantly lower in the cirrhotic rats than the control. None of the secretagogs induced the some amount of amylase release in cirrhotic as in control rats. Volume of the pancreatic juice and outputs of amylase and protein were significantly decreased under basal and cholecystokinin-8-stimulated conditions in vivo. Electron microscopy revealed most of the rough-surfaced endoplasmic reticulum accompanying less numbers of ribosomes to be dilated and some mitochondria to be swollen in cirrhotic rats. Conclusion Pancreatic exocrine functions are decreased in cirrhotic rats owing to alterations at the electron microscopic levels, reflecting an impaired acinar intracellular messenger system.     

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.     

Inhibitory effects of pirenzepine on cholecystokinin and secretin stimulation on exocrine and endocrine rat pancreas

Effects of pirenzepine, a newly developed anticholinergic drug, on exocrine and endocrine pancreatic functions stimulated by cholecystokinin octapeptide and secretin were studied in both isolated pancreatic acini and the isolated perfused pancreas of rats. In the isolated acini, pirenzepine did not have any significant effect on cholecystokinin-inducec amylase release but caused an inhibition of amylase secretion initiated by secretin and shifted the dose-response curve for amylase secretion to the right. In the isolated perfused pancreas stimulated with 100 pM cholecystokinin octapeptide, addition of 10 M pirenzepine before as well as after 20 min of perfusion significantly inhibited pancreatic juice flow but not enzyme output. In contrast, pirenzepine caused an inhibition of secretin-stimulated enzyme secretion, but not pancreatic juice flow. The stimulatory effect of both cholecystokinin octapeptide and secretin on insulin secretion was also inhibited by pirenzepine. The present data indicate that pirenzepine may have an influence on pancreatic exocrine and endocrine function by inhibiting endogenous cholinergic activity of the pancreas when a large dose is given.     

Exogenous administration of estradiol and cholecystokinin alters exocrine pancreatic function in rats

Summary This study was conducted in rats to investigate the influence of exogenously administered estradiol (ESD) and/or cholecystokinin (CCK) on components and secretions of the pancreatic acini. Intact male rats were treated for 14 d with exogenous administration of ESD, CCK, or ESD+CCK. After 14 d CCK treatment induced significant increases in DNA and RNA contents, and DNA/RNA ratio in the pancreas, indicating hyperplasia and hypertrophy of the pancreas, however, ESD treatment did not have these effects. Both ESD treatment and CCK treatment induced significant increases in amylase and trypsinogen contents in pancreatic acini and each decreased secretion from acini in response to CCK. Combined treatment with ESD plus CCK augmented these effects on enzyme contents and secretion. The results indicate that exogenous administration of CCK has trophic effects on the exocrine pancreas, increasing effects on enzyme contents and inhibitory effects on amylase secretion. In contrast, exogenous administration of ESD had no trophic effects on pancreas, but had increasing effects on enzyme contents and inhibitory effects on amylase secretion. The results suggest that the effects of exogenous ESD and CCK on pancreas are not similar to each other, but both ESD and CCK may be involved in regulating pancreatic exocrine functions.     

Regulation of intestinal concentration of cholecystokinin by bile and/or pancreatic juice

Pancreatic exocrine secretion in conscious rats is regulated by intraluminal bile and/or pancreatic juice. Exclusion of bile and/or pancreatic juice from the intestinal lumen caused cholecystokinin (CCK) release and stimulated pancreatic secretion. CCK in the plasma is mainly derived from endocrine cells in the proximal small intestinal mucosa. We examined the changes in CCK concentrations in the intestinal mucosa and compared them to those of plasma CCK concentrations and the changes of luminal trypsin activities after bile and/or pancreatic juice diversion in conscious rats. Rats with bile and pancreatic fistulae were used. Each treatment of bile, pancreatic juice, and bile-pancreatic juice diversion decreased luminal trypsin activity and increased plasma and intestinal CCK concentrations. The potency of the stimulatory effect on plasma and intestinal CCK concentrations was bilepancreatic juice diversion>pancreatic juice diversionbile diversion. Neither plasma CCK concentration nor intestinal CCK concentration was in inverse proportion to trypsin activity. The plasma CCK concentration did not parallel intestinal CCK concentration. Intravenous infusion of CCK-8 (300 pmol/kg/hr) did not increase CCK concentration in the intestinal mucosa. It was proposed that bile and/or pancreatic juice in the intestinal lumen regulated CCK concentrations not only in the plasma but also in the intestinal mucosa.     

Gallbladder dynamics in chronic pancreatitis

Gallbladder dynamics, cholecystokinin (CCK), and pancreatic polypeptide (PP) release were studied in 14 patients with chronic pancreatitis (CP) (2 females, 12 males; age range 24–56 years) and 12 control subjects (4 females, 8 males, 21–50 years). On day 1, gallbladder contractility was investigated after ceruletide intravenous infusion (2.5 ng/kg/min for 10 min). On day 2, a mixed standard test meal (1450 kJ) was administered orally. Gallbladder volume was assessed at three time intervals before (–30, –15, 0 min) and at 5, 10, 20, 30, 40, 50, 60, 80, 100 and 120 min after stimulation by means of ultrasonography. CCK and PP plasma levels were determined at each time interval.Exocrine pancreatic function was assessed using the pancreolauryl serum test (PLT). Six patients with CP had severe exocrine pancreatic insufficiency (EPI) (PLT<1.8 g/ml) with steatorrhea, eight patients had mild-moderate EPI. Fasting gallbladder volume was increased in CP (32.3±3.1 cm³) as compared to controls (20.5±1.2 cm³) (P<0.01). Peak gallbladder contraction (percent of initial volume) in CP ranged from 5 to 55% (controls: 8–46%) following ceruletide and from 17 to 86% (controls: 27–80%) following the test meal (NS). There was no correlation between the degree of EPI according to PLT and peak gallbladder contraction. Gallbladder emptying in CP patients was not different from controls, although the postprandial CCK response was significantly impaired (P<0.01). Postprandial PP response in CP was correlated with the PLT result (r=0.78;P<0.01) but not with gallbladder emptying or refilling time. We conclude that gallbladder emptying and refilling following the oral administration of a test meal or the stimulation with a pharmacological dose of ceruletide is normal in patients with chronic pancreatitis. Postprandial gallbladder emptying is not influenced by the degree of exocrine pancreatic insufficiency.     

Effects of tetraprenylacetone on pancreatic exocrine secretion and acute pancreatitis in two experimental models in rats

Summary The effects of tetraprenylacetone (TPN), an acyclic polyisoprenoid with antiulcer actions, on pancreatic exocrine secretion, and its preventive and therapeutic effects on acute pancreatitis in two experimental models were studied in rats. Intraduodenal administration of TPN (0, 100, 200 and 400 mg/kg/h) caused dose-dependent increases in pancreatic juice and bicarbonate output without increasing protein output and plasma cholecystokinin (CCK) concentrations. TPN-stimulated pancreatic exocrine secretion was completely abolished by antisecretin serum but it was not by CCK receptor antagonist loxiglumide (50 mg/kg/h). In acute pancreatitis induced by four subcutaneous injections of 20 μg/kg cerulein at hourly intervals over, 3 h, TPN (400 mg/kg) given by an oral route either 1 h before the first cerulein injection or immediately after the last injection significantly reduced the increases in serum amylase and lipase activities and pancreatic wet wt. Pretreatment with TPN caused histologic improvements, whereas posttreatment failed to ameliorate histologic alterations. In severe type of acute pancreatitis induced by retrograde intraductal injection of 1.0 mL/kg of 4% sodium taurocholate, TPN exerted no apparent beneficial effects on biochemical and histologic alterations of acute pancreatitis. It is concluded that TPN given by an oral route stimulates pancreatic exocrine secretion through an increase in endogenous secretin release and causes beneficial effects on the experimental model of mild acute pancreatitis in rats.     

Effects of a new benzodiazepine derivative cholecystokinin receptor antagonist FK480 on pancreatic exocrine secretion in anesthetized rats

Inhibitory effects of a newly developed benzodiazepine derivative (S)-N-[1-(2-fluorophenyl)-3,4,6,7-tetrahydro-4-oxo-pyrrolo-[3,2,1-jk][1,4] benzodiazepine-3yl]-1H-indole-2-carboxamide (FK480), a cholecystokinin (CCK) -A receptor antagonist, on pancreatic exocrine secretion were examinedin vivo in anesthetized rats. The antagonism produced by FK480 was competitive in nature because intraduodenal as well as intravenous infusion of FK480 (50–250 nmol/kg/hr) caused a parallel rightward shift of the entire dose-response curve for cerulein-stimulated pancreatic exocrine secretion without altering the maximal increase. The magnitude of the shift was proportional to the dose of FK480. The mean pA2 and ID₅₀ values of intravenously administered FK480 were 8.2 and 24 nmol/kg/hr, respectively, and those of intraduodenally infused FK480 were 7.7 and 168 nmol/kg/hr, respectively. Thus, FK480 given by the intravenous route was about sevenfold more potent than that given by the oral route. The antagonistic effects produced by intravenous FK480 were specific for CCK receptor in that the stimulatory effects of cerulein were inhibited whereas those of bombesin and secretin were not altered. In addition, intravenous administration of 50 nmol/kg/hr FK480 completely suppressed pancreatic exocrine secretion in response to intraduodenal infusion of 10% casein (400 mg/hr). FK480 was active as a CCK receptor antagonist for more than 12 hr because oral administration of FK480 (1.0 mg/kg) had significant inhibitory effects even after 12 hr on cerulein-stimulated pancreatic exocrine secretion. These results indicate that FK480 is a potent, competitive, and specific CCK receptor antagonist on the exocrine pancreasin vivo, having oral bioavailability and a long biological half-life.This work was supported in part by a grant from the Japanese Ministry of Health and Welfare (Intractable Disease of the Pancreas).     

Bile acids in human plasma interfere with cholecystokinin bioassay using dispersed pancreatic acini

A bioassay using dispersed pancreatic acini was used to measure fasting plasma cholecystokinin (CCK) concentrations in 105 patients with various kinds of gastrointestinal diseases, 17 patients with diabetes mellitus, and 6 healthy voluntters. High plasma CCK bioactivities were observed in patients with obstructive jaundice, choledocolithiasis, and primary biliary cirrhosis. Twenty-three samples with high CCK bioactivities were assayed by the same bioassay after the addition of a specific CCK antagonist and by a CCK radioimmunoassay in order to determine whether the high CCK-like bioactivity was due to circulating CCK or other factors. High CCK bioactivities were partially inhibited by the specific CCK antagonist, CR-1409, but the activities were not totally abolished. The residual bioactivities (not inhibited by CR-1409) correlated with plasma bile acid concentrations. The inhibitable CCK bioactivities correlated with plasma CCK levels obtained by radioimmunoassay. Although the bioassay using dispersed pancreatic acini has several advantages for measuring plasma CCK, this method overestimates CCK bioactivities in patients with high plasma bile acid concentrations.     

The influence of cutting the pancreatic nerve plexus on exocrine function in the pancreas of rats

This study was performed to clarify changes in protein synthesis and exocrine enzymes of the pancreas after cutting the pancreatic nerve plexus of Wistar rats. The rats were divided into two groups, consisting of a group that underwent cutting of the pancreatic nerve plexus (neurotomy group) and a group that underwent a sham operation (control group).³H-leucine uptake in the pancreatic protein fraction of the neurotomy group at 3, 5 and 7 days after the operation was significantly lower than that of the control group (P<0.05-0.01), and this low uptake returned to the normal range at 14 days. Amylase, lipase and trypsin values in pancreatic tissue of the neurotomy group decreased during the period of from 1 to 7 days, and there were significant differences in the values of the respective enzymes at 5 or 7 days between the neurotomy and the control group (P<0.05). Thereafter, all enzyme values increased to within the normal range. Upon examination of pancreatic blood flow using a microsphere, the neurotomy group showed a significant reduction at 7 days compared with the control group (P<0.05), and thereafter exhibited recovery of blood flow. These results indicate that after cutting the pancreatic nerve plexus, exocrine function in the pancreas is reduced immediately but recovers within a short period of time, and that these changes in exocrine function are affected by blood flow in the pancreas. Supported partially by the grants from the Japanese Ministry of Health & Welfare.     

Effect of atropine on responses of exocrine pancreas and plasma cholecystokinin to intraduodenal amino acids in dogs

The effect of atropine on responses of exocrine pancreas and plasma cholecystokinin (CCK) to intraduodenal mixed amino acids has been studied in conscious dogs with Thomas gastric and duodenal fistulae. Intraduodenal amino acids provoked significant increase of pancreatic protein output and of plasma CCK concentration. Atropine significantly reduced protein output only in the initial peak after amino acid administration. Atropine had no significant effect on plasma CCK. It is indicated that cholinergic nerves predominate in the early pancreatic protein response to intraduodenal amino acids and CCK prevails in the later phase, though these two factors do not seem to be the only factors responsible for the secretion.     

Effect of intraduodenai infusion of tocamphyl on pancreatic exocrine secretion and gastrointestinal hormone release in rats

Tocamphyl is a synthetic choleretic that is derived from a root extract ofCurcuma longa, L. We investigated the effect of tocamphyl on pancreatic exocrine secretion and bile flow, and on the release of some gastrointestinal hormones, by administering it intraduodenally using anesthetized rats. Tocamphyl stimulated pancreatic exocrine secretion in terms of volume and amylase output in a dose-related manner. Neither a CCK-receptor antagonist, CR1505 (loxiglumide), nor atropine sulfate infused intravenously suppressed the stimulatory effects of tocamphyl on pancreatic exocrine secretion and bile flow. The stimulatory effect on bile flow was stronger than that on pancreatic exocrine secretion. Plasma secretin levels were augmented with the increasing doses of tocamphyl, but CCK levels were not. These results indicate that intraduodenally administered tocamphyl stimulates pancreatic exocrine secretion and bile flow, and suggest that the stimulatory action is, at least in part, mediated by secretin, but not by either CCK or the cholinergic pathway.     

The role of sphinter of Boyden in bile excretion and its regulating factors

AIM To investigate the role of sphincter of Boyden in bile excretion and its regulating factors.METHODS Perfusion manometry, choledocho-cineradiography, reaction of the sphincter of Boyden toendogenous cholecystokinin (CCK) and immunohistochemical quantitative analysis were performed in 16dogs to study the motility and morphology of the sphincter of Boyden in experimental (postcholecystectomy)group ( n = 8) and the control group (n = 8).RESULTS The bile duct surrounded by SB was a low-pressure lumen (10.0 ± 2.0 mmHg), in which thepressure was significantly different (P<0.01, t = 6. 195) from the basal pressure of the high-pressure area ofsphincter of Oddi (SO), its basal pressure (SOBP) was 16.9±0.5 mmHg. The SB was an enlarged ampulladuring bile excretion interval, and showed active contraction during bile excretion. Intrinsic CCK could causediastole of SO, but does not affect the systole and diastole of SB. After cholecystectomy, spastic contractionpersisted in SB, which could not be relieved by intrinsic CCK. The sensitivity to CCK of SO was decreased,and the evacuation time of media prolonged (27.0±3.4 min vs precholecystectomy 17.l±0.9min P<0.01,t =7.961). In immunohistochemistry analysis, the contents of a-actin, myosin in the SB of experimentalgroup showed no increase. Under electronic microscope, the main changes were 3D structuraldisarrangement of the cell framework, distortion of the microfilaments, swelling and aggregation ofmitochondria at the nuclear side.CONCLUSION The excretion of bile can be divided into two types, physiological bile excretion with a drivemainly caused by the contraction of SB, and the other, functional bile excretion with a drive mainly causedby the contraction of gallbladder. It seems that the function of SB was controlled by vagus, whereas SO wasmore sensitive to the intrinsic CCK, The intact gallbladder is an elemental factor of functional coordinationof SB and SO.     

Exocrine function of caerulein-induced acute pancreatitis in anesthetized rats

Exocrine function was studied in anesthetized rats that had received two specific doses of caerulein (maximal stimulation and supramaximal stimulation). Male Wistar rats (body weight, 200–250 g) were divided into three groups: the control group (4-h saline infusion), the maximal stimulation group (0.25 g/kg per h caerulein for 4 h), and the caerulein pancreatitis group (10g/kg per h for 4 h). Histologically, inter-stitial edema and cytoplasmic vacuolization were observed only in the caerulein pancreatitis group, with no abnormal findings in the other groups. The volume of pancreatic juice was significantly increased in both the maximal stimulation group and the caerulein pancreatitis group. The protein ouput and the amylase output in the 1st h of caerulein infusion were also significantly increased, to 459% and 338% in the maximal stimulation group, and to 925% and 1430% respectively, in the caerulein pancreatitis compared to the baseline values. We also found that the pancreatic juice of the caerulein pancreatitis group contained precipitated protein, and high trypsin activity, and protein degradation was confirmed by electrophoresis. These findings were not observed in the other groups. These results strongly suggest that hypersecretion and the appearance of trypsin activity in pancreatic juice plays an important role in the induction of histological changes in this pancreatitis model in anesthetized rats.