scholarly journals Mechanism of bile salt-induced mucin secretion by cultured dog gallbladder epithelial cells

1996 ◽  
Vol 316 (3) ◽  
pp. 873-877 ◽  
Author(s):  
J. Henriëtte KLINKSPOOR ◽  
Guido N. J. TYTGAT ◽  
Sum P. LEE ◽  
Albert K. GROEN
Keyword(s):  
Epithelial Cells ◽  
Bile Salt ◽  
Bile Salts ◽  
Cholesterol Gallstone ◽  
Direct Interaction ◽  
Gallstone Formation ◽  
Intracellular Camp ◽  
Mucin Secretion ◽  
Camp Content ◽  
Intracellular Camp Content

1. Hypersecretion of gallbladder mucin has been proposed to be a pathogenic factor in cholesterol gallstone formation. Using cultured gallbladder epithelial cells, we demonstrated that bile salts regulate mucin secretion by the gallbladder epithelium. In the present study we have investigated whether established second messenger pathways are involved in bile salt-induced mucin secretion. 2. The effect of activators and inhibitors on mucin secretion was studied by measuring the secretion of [3H]N-acetyl-D-glucosamine-labelled glycoproteins. Intracellular cAMP content of the cells was measured using a radioimmunoassay. 3. Incubation of the cells with 10 mM taurocholate did not increase the intracellular cAMP content (25.7 versus control 22.8 pmol of cAMP/mg of protein). No stimulation of mucin secretion was observed after incubation with 1–100 μM concentrations of the calcium ionophores ionomycin and A23187. The stimulatory effect of 10 mM tauroursodeoxycholate (TUDC) on mucin secretion could not be inhibited by the addition of EDTA. Activation of protein kinase C (PKC) by 1 μg/ml phorbol 12-myristate 13-acetate (PMA) caused an increase in mucin secretion (342% versus control 100%), comparable with the effect of 40 mM TUDC. The effect of 10 ng/ml PMA could partially be inhibited by a concentration of 2 μM of the PKC inhibitor staurosporin. Staurosporin had no inhibitory effect on mucin secretion induced by TUDC. 4. In gallbladder epithelial cells bile salts do not stimulate mucin secretion via one of the classical signal transduction pathways. We hypothesize that bile salts act on mucin secretion via a direct interaction with the apical membrane.

PGE generates intracellular cAMP and accelerates mucin secretion by cultured dog gallbladder epithelial cells

1994 ◽  
Vol 267 (6) ◽  
pp. G998-G1003 ◽  
Author(s):  
R. Kuver ◽  
C. Savard ◽  
D. Oda ◽  
S. P. Lee
Keyword(s):  
Epithelial Cells ◽  
Second Messengers ◽  
Signal Transduction Pathway ◽  
Fold Increase ◽  
Gallstone Formation ◽  
Intracellular Camp ◽  
Secretory Product ◽  
Mucin Secretion ◽  
Pg E2 ◽  
Well Differentiated

Mucin is the main secretory product of gallbladder epithelial cells. Increased gallbladder mucus secretion has been implicated in gallstone formation in humans. The mechanisms underlying control of mucin synthesis and secretion by the gallbladder are not known. This study aimed to elucidate the efficacy of a panel of secretagogues to stimulate mucin secretion and to determine the intracellular second messengers involved. Studies were carried out on normal well-differentiated epithelial cells from dog gallbladder grown in monolayer culture. Intracellular adenosine 3',5'-cyclic monophosphate (cAMP) as measured by radioimmunoassay increased in response to prostaglandin (PG) E2, PGE1, vasoactive intestinal peptide, epinephrine, and isoproterenol. The greatest effect, a 37-fold increase in cAMP level, was noted with PGE2 at 1.0 microM concentration. In contrast, three breakdown products of phosphatidylinositol (inositol triphosphate, inositol bisphosphate and inositol monophosphate) were not detected with any of the secretagogues tested. Assay of mucin secretion using tritiated N-acetyl-D-glucosamine, a mucin precursor, showed that the same secretagogues noted to increase intracellular cAMP led to an increase in mucin secretion. No correlation was noted, however, between the magnitude of the intracellular cAMP rise and the amount of mucin secreted. A membrane-permeable form of cAMP, dibutyryl cAMP, mimicked PGE2-induced mucin secretion. The results unequivocally show that secretagogue-stimulated mucin secretion in these normal gallbladder epithelial cells can proceed via a cAMP signal transduction pathway.

Effects of PGI2 and Its More Stable Forms on the Aggregation and on the Camp Content of Human Platelets

1979 ◽  
Author(s):  
E. Nemesánszky ◽  
I. Blaskó ◽  
I. Stadler ◽  
G. Sas ◽  
L. A. Pálos
Keyword(s):  
Ethyl Ester ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Intracellular Camp ◽  
Camp Content ◽  
Prolonged Duration ◽  
Potent Inhibitory Effect ◽  
Stable Forms ◽  
Derivatives Of ◽  
Intracellular Camp Content

The authors investigated the anti-aggregating properties of some relatively stable derivatives of PGI2 concurrently determining the intracellular cAMP content of platelets. The ethyl-ester derivative of PGI2 and the complexes of PGI2-ethyl ester with β-cyclodextrine proved to be more stable than PGI2-sodium salt. Their stimulating effect on adenyl-cyclase correlated with the potent inhibitory effect on platelet aggregation as well. The enhancing effect of these compounds for the intracellular cAMP content have a prolonged duration time -lasting 300 minutes- compared with the only a few minutes’ effect of PGE1.These stable forms of PGI2 might be clinically useful as highly effective antiaggregating compounds.

scholarly journals Naringenin Regulates CFTR Activation and Expression in Airway Epithelial Cells

2017 ◽  
Vol 44 (3) ◽  
pp. 1146-1160 ◽  
Author(s):  
Rui Shi ◽  
Zi-Ting Xiao ◽  
Yi-Jun Zheng ◽  
Yi-Lin Zhang ◽  
Jia-Wen Xu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Short Circuit ◽  
Short Circuit Current ◽  
The Elderly ◽  
Airway Epithelial Cells ◽  
Intracellular Camp ◽  
Transmembrane Conductance Regulator ◽  
Airway Epithelial ◽  
Camp Content ◽  
Basolateral Side

Background/Aims: Sputum symptoms are commonly seen in the elderly. This study aimed to identify an efficacious expectorant treatment stratagem through evaluating the secretion-promoting activation and cystic fibrosis transmembrane conductance regulator (CFTR) expression of the bioactive herbal monomer naringenin. Methods: Vectorial Cl- transport was determined by measuring short-circuit current (ISC) in rat airway epithelium. cAMP content was measured by ELISA in primary cultured epithelial cells and Calu-3 cells. CFTR expression in Calu-3 cells was determined by qPCR. Results: Addition of naringenin to the basolateral side of the rat airway led to a concentration-dependent sustained increase in ISC. The current was suppressed when exposed to Cl–-free solution or by bumetanide, BaCl2, and DPC but not by DIDS and IBMX. Forskolin-induced ISC increase and CFTRinh-172/MDL-12330A-induced ISC inhibition were not altered by naringenin. Intracellular cAMP content was significantly increased by naringenin. With lipopolysaccharide stimulation, CFTR expression was significantly reduced, and naringenin dose-dependently enhanced CFTR mRNA expression. Conclusion: These results demonstrate that naringenin has the ability to stimulate Cl- secretion, which is mediated by CFTR through a signaling pathway by increasing cAMP content. Moreover, naringenin can increase CFTR expression when organism CFTR expression is seriously hampered. Our data suggest a potentially effective treatment strategy for sputum.

scholarly journals Metastable and equilibrium phase diagrams of unconjugated bilirubin IXα as functions of pH in model bile systems: Implications for pigment gallstone formation

2015 ◽  
Vol 308 (1) ◽  
pp. G42-G55 ◽  
Author(s):  
Marvin D. Berman ◽  
Martin C. Carey
Keyword(s):  
Phase Diagrams ◽  
Bile Salts ◽  
Cholesterol Gallstone ◽  
Equilibrium Phase ◽  
Gallstone Formation ◽  
Unconjugated Bilirubin ◽  
Ph Values ◽  
Wide Range ◽  
Pigment Gallstone ◽  
Model Bile

Metastable and equilibrium phase diagrams for unconjugated bilirubin IXα (UCB) in bile are yet to be determined for understanding the physical chemistry of pigment gallstone formation. Also, UCB is a molecule of considerable biomedical importance because it is a potent antioxidant and an inhibitor of atherogenesis. We employed principally a titrimetric approach to obtain metastable and equilibrium UCB solubilities in model bile systems composed of taurine-conjugated bile salts, egg yolk lecithin (mixed long-chain phosphatidylcholines), and cholesterol as functions of total lipid concentration, biliary pH values, and CaCl2 plus NaCl concentrations. Metastable and equilibrium precipitation pH values were obtained, and average pKa values of the two carboxyl groups of UCB were calculated. Added lecithin and increased temperature decreased UCB solubility markedly, whereas increases in bile salt concentrations and molar levels of urea augmented solubility. A wide range of NaCl and cholesterol concentrations resulted in no specific effects, whereas added CaCl2 produced large decreases in UCB solubilities at alkaline pH values only. UV-visible absorption spectra were consistent with both hydrophobic and hydrophilic interactions between UCB and bile salts that were strongly influenced by pH. Reliable literature values for UCB compositions of native gallbladder biles revealed that biles from hemolytic mice and humans with black pigment gallstones are markedly supersaturated with UCB and exhibit more acidic pH values, whereas biles from nonstone control animals and patients with cholesterol gallstone are unsaturated with UCB.

Model bile and bile salts accelerate mucin secretion by cultured dog gallbladder epithelial cells

1995 ◽  
Vol 109 (1) ◽  
pp. 264-274 ◽  
Author(s):  
J.Henriëtte Klinkspoor ◽  
Rahul Kuver ◽  
Christopher E. Savard ◽  
Dolphine Oda ◽  
Hanna Azzouz ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bile Salts ◽  
Mucin Secretion ◽  
Model Bile
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