vasoactive-intestinal-peptide and Gallstones

To investigate the mechanisms and effects of sphincter of Oddi (SO) motility on cholesterol gallbladder stone formation in guinea pigs.. Thirty-four adult male Hartley guinea pigs were divided randomly into two groups, the control group (n = 10) and the cholesterol gallstone group (n = 24), which was sequentially divided into four subgroups with six guinea pigs each according to time of sacrifice. The guinea pigs in the cholesterol gallstone group were fed a cholesterol lithogenic diet and sacrificed after 3, 6, 9, and 12 wk. SO manometry and recording of myoelectric activity were obtained by a multifunctional physiograph at each stage. Cholecystokinin-A receptor (CCKAR) expression levels in SO smooth muscle were detected by quantitative real-time PCR (qRT-PCR) and serum vasoactive intestinal peptide (VIP), gastrin, and cholecystokinin octapeptide (CCK-8) were detected by enzyme-linked immunosorbent assay at each stage in the process of cholesterol gallstone formation.. The gallstone formation rate was 0%, 0%, 16.7%, and 83.3% in the 3, 6, 9, and 12 wk groups, respectively. The frequency of myoelectric activity in the 9 wk group, the amplitude of myoelectric activity in the 9 and 12 wk groups, and the amplitude and the frequency of SO in the 9 wk group were all significantly decreased compared to the control group. The SO basal pressure and common bile duct pressure increased markedly in the 12 wk group, and the CCKAR expression levels increased in the 6 and 12 wk groups compared to the control group. Serum VIP was elevated significantly in the 9 and 12 wk groups and gastrin decreased significantly in the 3 and 9 wk groups. There was no difference in serum CCK-8 between the groups.. A cholesterol gallstone-causing diet can induce SO dysfunction. The increasing tension of the SO along with its decreasing activity may play an important role in cholesterol gallstone formation. Expression changes of CCKAR in SO smooth muscle and serum VIP and CCK-8 may be important causes of SO dysfunction.

Topics: Animals; Cholesterol; Disease Models, Animal; Electromyography; Enzyme-Linked Immunosorbent Assay; Gallstones; Gastrins; Guinea Pigs; Manometry; Muscle, Smooth; Real-Time Polymerase Chain Reaction; Receptor, Cholecystokinin A; Sincalide; Sphincter of Oddi; Sphincter of Oddi Dysfunction; Vasoactive Intestinal Peptide

To investigate roles of sphincter of Oddi (SO) motility played in pigment gallbladder stone formation in model of guinea pigs.. Thirty-four adult male Hartley guinea pigs were divided randomly into two groups: the control group and pigment stone group. The pigment stone group was divided into 4 subgroups with 6 guinea pigs each according to time of sacrifice, and were fed a pigment lithogenic diet and sacrificed after 3, 6, 9 and 12 wk. SO manometry and recording of myoelectric activity of the guinea pigs were obtained by multifunctional physiograph at each stage. Serum vasoactive intestinal peptide (VIP), gastrin and cholecystokinin octapeptide (CCK-8) were detected at each stage in the process of pigment gallbladder stone formation by enzyme-linked immunosorbent assay.. The incidence of pigment gallstone formation was 0%, 0%, 16.7% and 66.7% in the 3-, 6-, 9- and 12-wk group, respectively. The frequency of myoelectric activity decreased in the 3-wk group. The amplitude of myoelectric activity had a tendency to decrease but not significantly. The frequency of the SO decreased significantly in the 9-wk group. The SO basal pressure and common bile duct pressure increased in the 12-wk group (25.19 ± 7.77 mmHg vs 40.56 ± 11.81 mmHg, 22.35 ± 7.60 mmHg vs 38.51 ± 11.57 mmHg, P < 0.05). Serum VIP was significantly elevated in the 6- and 12-wk groups and serum CCK-8 was decreased significantly in the 12-wk group.. Pigment gallstone-causing diet may induce SO dysfunction. The tension of the SO increased. The disturbance in SO motility may play a role in pigment gallstone formation, and changes in serum VIP and CCK-8 may be important causes of SO dysfunction.

Topics: Animals; Cholestasis; Disease Models, Animal; Gallstones; Gastrins; Guinea Pigs; Male; Manometry; Membrane Potentials; Pressure; Sincalide; Sphincter of Oddi; Time Factors; Vasoactive Intestinal Peptide

The disorders of gallbladder motility may play an important role in the formation of gallstones. Many neural and hormonal factors and their interactions regulate gallbladder motility and bile flow into the duodenum. Further study in these factors may help to reveal the etiology of gallbladder diseases. This study was undertaken to assess the relationship of the levels of motilin, vasoactive intestinal peptide (VIP) and gastrin in blood and gallbladder tissues with the formation of cholelithiasis.. The levels of motilin, gastrin and VIP in blood and gallbladder tissues of 36 patients with gallbladder stones, 14 patients with gallbladder polyps, 10 healthy volunteers and 10 patients with common bile duct stones were measured by radioimmunoassay.. The level of motilin in plasma and gallbladder tissues of the gallbladder stone group was higher than that of the control and gallbladder polyp groups (P<0.05). The levels of plasma VIP and serum gastrin were much higher than those of the other three groups (P<0.01). The level of VIP in gallbladder tissues was higher than that of the control and gallbladder polyp groups (P<0.01).. The abnormal excretion of hormonal factors is closely related to gallstone formation. The high level of VIP in gallbladder tissues may be an important cause of gallbladder hypomotility. The abnormal level of serum gastrin may be related to the gastrointestinal symptoms of patients with gallstones.

Topics: Common Bile Duct; Female; Gallbladder; Gallstones; Gastrins; Gastrointestinal Hormones; Humans; Male; Middle Aged; Motilin; Polyps; Vasoactive Intestinal Peptide

The morphology of tryptase-, and vasoactive intestinal polypeptide (VIP)-positive mast cells was examined immunohistochemically in 38 common bile ducts collected from patients with secondary chronic cholangitis and varying degrees of inflammatory activity. Mast cells numbers in chronic exacerbated and chronic sclerotic cholangitis were significantly higher as compared with those in controls (72.4 cells/mm2 and 25.2 cells/mm2 vs. 5.9 cells/mm2; p < 0.0001, Student's t test). The increased number of tryptase-positive mast cells in chronic exacerbated cholangitis correlated with the severeness of inflammatory infiltration. In cases of chronic exacerbated cholangitis, the increased number of mast cells was detected in conjunction with active fibroplasia. In chronic sclerotic cholangitis mast cells were lower in number as compared with exacerbated cholangitis and were observed in relation with inactive fibrosis. Numerous VIP-positive mast cells were found in all patients with cholangitis. Ultrastructural immunocytochemistry showed tryptase positivity to be localized over either electron-dense or particulate granules with a mean diameter of 0.261+/-0.073 microm or 0.171+/-0.053 microm, respectively. VIP positivity was formed as a finely or coarsely granular pattern over larger electron-dense granules of 0.475+/-0.14 microm in diameter. Tryptase-positive mast cells were located mainly in and around surface and glandular epithelium. The involvement of tryptase- and VIP-positive mast cells in inflammation, fibrosis and epithelial reactions in the common bile duct is discussed.

Topics: Adult; Aged; Aged, 80 and over; Cholestasis; Female; Gallstones; Humans; Male; Mast Cells; Middle Aged; Serine Endopeptidases; Tryptases; Vasoactive Intestinal Peptide

The aim of the present work was to study the effect of substance P (SP) and somatostatin (SST) on hepatic bile flow. For this purpose a total of 54 anesthetized mongrel dogs were used. The gallbladder was excluded by ligation of the cystic duct and a common duct fistula was created by insertion of a catheter into the common duct. Both SP and SST were found to exert an anticholeretic effect in the dog. SST was also found to be anticholeretic in man. In the dog, SP was infused at dosages from 0.5-20 ng kg-1 min-1 and exerted a significant anticholeretic effect at a dosage of 2.5 ng or higher. At dosages of 2.5 and 20 ng kg-1 min-1, SP decreased the basal bile secretion by about 20 and 40% respectively. The decrease in bile flow was accompanied by decreased outputs of sodium, potassium, chloride, bicarbonate and amylase. With taurocholate-stabilized and taurocholate-stabilized and hormone-induced bile secretion, SP had the above mentioned effects and in addition the output of bile acids decreased. The effect of SP occurred within minutes and after withdrawal of SP there was a positive rebound effect, with a magnitude of about 30% following the 20 ng dosage. SST at dosages from 20-1000 ng kg-1 min-1 induced an anticholeretic effect with a magnitude of 10-25%. With both basal and taurocholate-stabilized bile secretion, the outputs of bile, bile acids and electrolytes decreased during the infusion period and remained diminished for 10-20 min after termination of the infusion. Unlike SP, SST had no anticholeretic effect in the presence of CCK or secretin. A simultaneous infusion of SP and SST decreased bile flow more than either agent alone. The anticholeretic effect of SST was verified in five patients. They had all been operated on for choledocholithiasis. In four patients a complete diversion of bile was obtained with a Foley catheter in the common duct and in the fifth patient from an impacted stone in the common duct. During infusion of SST, 250 ug h-1, the outputs of hepatic bile and bile acids decreased while the outputs of cholesterol and phospholipids were unchanged. The serum bile acid concentration was unaffected by SST and therefore SST is suggested to exert an inhibitory effect on bile acid synthesis. The changes in electrolyte outputs induced by SST in man corresponded to those in the dog.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Amylases; Animals; Bicarbonates; Bile; Bile Acids and Salts; Cholecystokinin; Cholesterol; Dogs; Dose-Response Relationship, Drug; Gallstones; Humans; Hydrogen-Ion Concentration; Phospholipids; Potassium; Secretin; Sodium; Somatostatin; Substance P; Taurocholic Acid; Vasoactive Intestinal Peptide