vasoactive-intestinal-peptide and Cholestasis

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

Surgical biopsy specimens obtained from 50 patients with secondary cholangitis caused by obstruction of the common bile duct were studied immunohistochemically. Data on the number and ultrastructural appearances of mast cells positive for tryptase, chymase, vasointestinal polypeptide (VIP), and substance P (SP) were obtained. The bile ducts from patients presenting combined chronic exacerbated cholangitis and chronic sclerotic cholangitis showed significantly higher numbers of mast cell types compared to the controls (P < 0.0001). Cases with sclerotic cholangitis alone had significantly lower number of cells than patients with chronic exacerbated cholangitis alone (P < or = 0.0001). Morphometric measurements of electron micrographs showed that mast cell granules containing VIP, SP and chymase were commensurable in size. Electron-lucent granules without reaction product (altered granules) and granules with focal distribution of the reaction product were observed in all types of mast cells. Furthermore, some nerve fibers positive for SP and VIP and serotonin-positive endocrine cells were observed in close proximity to the mast cells. In conclusion, the results of our study demonstrate the existence of different populations of mast cells, nerve structures and endocrine cells in the lower part of the human large bile duct, and suggest their participation in the development of pathological processes.

Topics: Adult; Aged; Aged, 80 and over; Bile Ducts; Biopsy; Cholangitis; Cholestasis; Chymases; Female; Humans; Male; Mast Cells; Middle Aged; Serine Endopeptidases; Serotonin; Substance P; Tryptases; 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

Liver proliferation appears to be dually regulated, in part by cyclic AMP levels. Here we studied the alterations in the stimulatory action of cholera toxin and other agents on the adenylyl cyclase system, as well as the status of Gs and Gi protein subunits during the liver proliferation that follows bile duct ligation in rats. The stimulatory effects of glucagon and vasoactive intestinal peptide (which act through membrane receptors) or guanosine 5'-[beta gamma-imido]triphosphate (which interacts with G proteins) and forskolin (which directly activates the adenylyl cyclase catalytic subunit) on liver adenylyl cyclase activity were blunted in cholestasis. The results indicated an impairment in the stimulatory interaction between the alpha s subunit of Gs protein and the adenylyl cyclase catalytic subunit. Indeed, we observed an important decrease in the stimulation of adenylyl cyclase activity by cholera toxin in cholestasis that was accompanied by a reduced extent of [32P]ADP ribosylation of alpha s protein catalyzed by cholera toxin, as revealed by the poor labeling of the 42,000 Da band in liver membranes from cholestatic rats. However, there was no change in the amount of alpha s or beta proteins as measured with immunoblotting techniques. Experiments on [32P]ADP ribosylation of alpha i subunits of Gi proteins indicated an impairment in liver membranes from cholestatic rats, whereas Western blotting for the detection of alpha i subunits showed decreased alpha i3 and increased alpha i2 levels in this condition. Further efforts are needed to better understand the molecular mechanisms underlying the relationship between the observed divergent expression of Gs and Gi proteins and liver cell proliferation in the cholestatic liver.

Topics: Adenosine Diphosphate; Adenylate Cyclase Toxin; Adenylyl Cyclases; Animals; Bile Ducts; Cell Division; Cell Membrane; Cholera Toxin; Cholestasis; Colforsin; Glucagon; GTP-Binding Proteins; Guanylyl Imidodiphosphate; Ligation; Liver; Male; Peptide Fragments; Pertussis Toxin; Rats; Rats, Wistar; Vasoactive Intestinal Peptide; Virulence Factors, Bordetella