Active amino-acid and sugar uptake by gall bladder epithelium in dog, guinea-pig and man

Mirkovitch, V.; Sepúlveda, Francisco V.; Menge, H.; Robinson, J. W. L.

doi:10.1007/bf00579853

Cited by 14 publications

(3 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A similar metabolic effect of cytochalasin B is excluded as a possible cause of the inhibition of net fluid transport by rabbit gall-bladder. Firstly, it has been shown that, unlike other gallbladder epithelia, rabbit gall-bladder epithelium is incapable of active glucose uptake across the brush-border (Mirkovitch, Sepulveda, Menge & Robinson, 1975); secondly, the present data demonstrate that the effect is independent of the access to the substrates glucose, glutamate and pyruvate.…”

Section: Discussionsupporting

confidence: 43%

Effects of cytochalasin B and dimethylsulphoxide on isosmotic fluid transport by rabbit gall‐bladder in vitro.

Frederiksen¹,

Leyssac²

1977

The Journal of Physiology

View full text Add to dashboard Cite

SUMMARY1. Net fluid transport rate, transepithelial ohmic resistance and potential difference (p.d.), and unidirectional fluxes of Na+ were measured in rabbit gall-bladder preparations in vitro exposed on both sides to Ringer solutions of identical electrolyte composition. cytochalasin B on the active transcellular pump mechanism and to 0. FREDERIKSEN AND P. P. LEYSSAC suggest a cytochalasin B-mediated progressive increase in cell membrane permeability to sodium resulting ultimately in a highly leaky epithelium. The results are compatible with the concept that a mechanochemical process is involved in isosmotic transcellular transport of fluid across lowresistance epithelia.

show abstract

Section: Discussionsupporting

confidence: 43%

Effects of cytochalasin B and dimethylsulphoxide on isosmotic fluid transport by rabbit gall‐bladder in vitro.

Frederiksen¹,

Leyssac²

1977

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…In fact, phlorizin is known to inhibit Na + -glucose cotransport and Cl -/HCO 3 -exchange; however, since Na + -glucose cotransport is not present in rabbit gallbladder [29], in this epithelium the action of phlorizin is likely to be restricted to the anion exchange. Moreover, whereas the hydrophobic phloretin displays non-specific effects on the membrane lipid bilayer, thus increasing cation and decreasing anion conductances [1,5], the hydrophilic phlorizin does not cause these effects [26,27].…”

Section: Discussionmentioning

confidence: 96%

Inhibitors of the Cl - /HCO 3 - exchanger activate an apical anion conductance with similar features in the epithelial cells of rabbit gallbladder: analysis in intact epithelium

Cremaschi

Vallin

Sironi

et al. 2001

Pfl�gers Archiv European Journal of Physiology

View full text Add to dashboard Cite

In the apical plasma membrane of rabbit gallbladder epithelium, hydrochlorothiazide (HCTZ), besides its inhibiting action on Na+-Cl- symport and some side-effects, opens a SITS-sensitive Cl- conductance (Gcl), resulting in depolarization of the membrane due to a cell-to-lumen Cl- backflux. Some previous indications suggest that GCl is someway related to the Cl-/HCO3- exchanger. Thus the actions on the apical membrane of HCTZ and two inhibitors of the exchanger mainly studied in erythrocytes, namely phlorizin and phenylglyoxal (PG), have been compared. The transapical Cl- influx was measured radiochemically and the anion exchange fraction identified. The apical and transepithelial membrane potentials (Vm, Vm), the apical/basolateral membrane resistance ratio (Rm/Rs) and the transepithelial resistance (Rep) were measured with conventional microelectrodes and the changes in apical electromotive force and conductance were calculated. It has been shown that: (1) 2.5 x 10(-4) mol/l HCTZ abolishes Cl-/HCO3- exchange in a few seconds, (2) exchanger inhibition by HCTZ is direct and not mediated by carbonic anhydrase inhibition, (3) 2 mmol/l phlorizin and 4 mmol/l PG also inhibit the exchanger in a few seconds or at least rapidly and in parallel activate a depolarization of 6-7 mV, like HCTZ, (4) dose/response curves of the three drugs for depolarization activation and anion exchange inhibition overlap, (5) depolarization time courses are similar for the three drugs, (6) a decrease in the Rm/Rs ratio occurs in the presence of the three drugs, with a significant change in apical electromotive force when the luminal Cl- concentration is reduced, all this indicating the appearance of a substantial, quantifiable GCl which is absent in the absence of incubation with the drugs, (7) GCl values are similar, regardless of the drug which generates them, (8) the effects of the three drugs are not additive, and (9) stilbenes and dipyridamole abolish GCl (but not DPC) as well as the basal intrinsic conductance of the exchanger. On this basis it is concluded that some inhibitors of the Cl-/HCO3- exchanger either turn it into an anion channel or, less probably, activate a parallel GCl, as a consequence of the exchanger inhibition.

show abstract

“…Dog gallbladder mucosa is capable of reabsorbing amino acids by a sodium-dependent transport mechanism. However, when the common bile duct is ligated, amino acid uptake capacity is greatly reduced[ 32 ]. Accordingly, it is possible that stasis of bile, depletion of sodium content, or abnormal function of the gallbladder epithelium may contribute to loss of amino acids into the bile of dogs with mucocele formation.…”

Section: Discussionmentioning

confidence: 99%

Qualitative metabolomics profiling of serum and bile from dogs with gallbladder mucocele formation

et al. 2018

View full text Add to dashboard Cite

Mucocele formation is characterized by secretion of abnormally thick mucus by the gallbladder epithelium of dogs that may cause obstruction of the bile duct or rupture of the gallbladder. The disease is increasingly recognized and is associated with a high morbidity and mortality. The cause of gallbladder mucocele formation in dogs is unknown. There is a strong breed predisposition and affected dogs have a high incidence of concurrent endocrinopathy or hyperlipidemia. These observations suggest a significant influence of both genetic and metabolic factors on disease pathogenesis. In this study, we investigated a theory that mucocele formation is associated with a syndrome of metabolic disruption. We surmised that a global, untargeted metabolomics approach could provide unique insight into the systemic pathogenesis of gallbladder mucocele formation and identify specific compounds as candidate biomarkers or treatment targets. Moreover, concurrent examination of the serum and hepatic duct bile metabolome would enable the construction of mechanism-based theories or identification of specific compounds responsible for altered function of the gallbladder epithelium. Abnormalities observed in dogs with gallbladder mucocele formation, including a 33-fold decrease in serum adenosine 5’-monophosphate (AMP), lower quantities of precursors required for synthesis of energy transporting nucleotides, and increases in citric acid cycle intermediates, suggest excess metabolic energy and a carbon surplus. Altered quantities of compounds involved in protein translation and RNA turnover, together with accumulation of gamma-glutamylated and N-acetylated amino acids in serum suggest abnormal regulation of protein and amino acid metabolism. Increases in lathosterol and 7α-hydroxycholesterol suggest a primary increase in cholesterol synthesis and diversion to bile acid formation. A number of specific biomarker compounds were identified for their ability to distinguish between control dogs and those that formed a gallbladder mucocele. Particularly noteworthy was a significant decrease in quantity of biologically active compounds that stimulate biliary ductal fluid secretion including adenosine, cAMP, taurolithocholic acid, and taurocholic acid. These findings support the presence of significant metabolic disruption in dogs with mucocele formation. A targeted, quantitative analysis of the identified serum biomarkers is warranted to determine their utility for diagnosis of this disease. Finally, repletion of compounds whose biological activity normally promotes biliary ductal secretion should be examined for any therapeutic impact for resolution or prevention of mucocele formation.

show abstract

Active amino-acid and sugar uptake by gall bladder epithelium in dog, guinea-pig and man

Cited by 14 publications

References 12 publications

Effects of cytochalasin B and dimethylsulphoxide on isosmotic fluid transport by rabbit gall‐bladder in vitro.

Effects of cytochalasin B and dimethylsulphoxide on isosmotic fluid transport by rabbit gall‐bladder in vitro.

Inhibitors of the Cl - /HCO 3 - exchanger activate an apical anion conductance with similar features in the epithelial cells of rabbit gallbladder: analysis in intact epithelium

Qualitative metabolomics profiling of serum and bile from dogs with gallbladder mucocele formation

Contact Info

Product

Resources

About