Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cholates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed2001

Enhancement of absorption of insulin-loaded polyisobutylcyanoacrylate nanospheres by sodium cholate after oral and subcutaneous administration in diabetic rats.

Polyisobutylcyanoacrylate (PIBCA) nanospheres were employed as biodegradable polymeric carriers for oral (p.o.) and subcutaneous (s.c.) delivery of insulin. The polymerization technique used was able to hold 65%-95% of insulin added 30 min after initiation of polymerization. The percentage drug loading was monomer concentration dependent. Insulin adsorption to the nanospheres was measured by radioimmunoassay. Although Pluronic F68 (0.5%) did not significantly alter the in vitro insulin degradation half-life T50%, sodium cholate (0.5%) increased the degradation T50% of insulin by 56% (from 13.6 +/- 1.6 to 22.1 +/- 2 min). This study also investigated the in vivo performance of insulin-loaded PIBCA in aqueous suspension with or without sodium cholate (0.5%) and Pluronic F68 (0.5%) surfactants after oral and subcutaneous administration to alloxan-induced diabetic rats. Insulin absorption was evaluated by its hypoglycemic effect. Insulin associated with PIBCA nanospheres retains its biological activity up to 15 h and 24 h after oral and subcutaneous administrations, respectively. Administered orally insulin-loaded (75 U/kg) nanospheres, in the presence of surfactants, significantly reduced the mean blood glucose level from 392 +/- 32 to 80 +/- 13 mg/dl within 2 h and maintained it at 100 mg/dl or less for more than 8 h. On the other hand, the subcutaneous administration of insulin-loaded (25 U/kg) nanospheres significantly decreased the blood glucose level from 406 +/- 33 to 88.5 +/- 12.8 mg/dl within 1 h, and the lowered glucose level was maintained at 100 mg/dl or less for more than 12 h; it returned to its initial value 24 h after administration. Insulin-loaded nanospheres with surfactants showed significant (P < .05) pharmacological availability (PA%) of 37.6% +/- 3.7% and 65.2% +/- 2.7% after oral and subcutaneous dosages, respectively. The existence of surfactants with PIBCA nanospheres improved the oral PA% by 49.2%. These findings suggest that the developed PIBCA, in the presence of surfactants, would be useful not only in improving insulin gastrointestinal absorption, but also in sustaining its systemic action by lowering the blood glucose to an acceptable level.

Administration, Oral↗
PubMed1998

Hypoglycemic effect of oral insulin in diabetic rabbits using pH-dependent coated capsules containing sodium salicylate without and with sodium cholate.

The hypoglycemic effect of oral insulin (20 U and 40 U) capsules coated with a pH-dependent soluble polymer (Eudragit S100) and containing sodium salicylate (50 mg) without and with sodium cholate (50 mg) was studied in alloxan-hyperglycemic rabbits and compared with that of s.c. insulin injection (20 U). The capsules containing 20 U insulin + sodium salicylate (50 mg) produced a significant reduction in plasma glucose level to 82 and 73% of initial values at 2 and 3 hr after administration, respectively. The blood glucose level slowly returned to normal values at 5 hr. The AUC0-5 hr was 73.7 +/- 43.5 mg.hr/dl compared to 242 +/- 70.5 mg.hr/dl for insulin (20 U, s.c.) with a relative hypoglycemia of 30.4%. A higher dose of oral insulin (40 U) + sodium salicylate (50 mg) was more effective in reducing plasma glucose level which steadily decreased and reached 56% of the initial value by 5 hr (AUC0-5 hr = 132 +/- 41.5 mg.hr/dl and relative hypoglycemia = 27.3%). Sodium cholate (50 mg), however, slightly improved sodium salicylate effect producing an AUC0-5 hr of 139 +/- 37.3 mg.hr/dl with relative hypoglycemia of 28.7%. The relative hypoglycemia of pH-dependent coated capsules reached in the present experiment is the highest found so far.

Animals↗
PubMed1978

Light-scattering studies on bile acid salts I: Pattern of self-association of sodium cholate, sodium glycocholate, and sodium taurocholate in aqueous electrolyte solutions.

The pattern of association of the trihydroxy bile salts in aqueous electrolyte solutions was investigated utilizing the light-scattering technique. The turbidity of the bile salts sodium cholate, sodium taurocholate, and sodium glycocholate was determined over the concentration range of 0-25 mg/ml at 25 degrees. For sodium cholate, the concentration of the supporting electrolyte was varied from 0.15 to 0.5 M. For all bile salts in 0.15 M electrolyte, the turbidity was determined in sodium fluoride, sodium chloride, sodium bromide, and sodium iodide. Comparison of the light-scattering data with amonomer-micellar model showed that qualitative agreement was obtained; however, quantitative agreement could not be achieved. Further examination of the data showed that the light-scattering results were in good agreement with a model that includes dimers, trimers, and a higher aggregate containing approximately eight monomeric units.

Chemical Phenomena↗
PubMed1994

Cholate and pH reduce interference by sodium dodecyl sulfate in the determination of DNA with Hoechst.

The use of the fluorescent dye 33258 Hoechst (Hoe) to quantitatively determine DNA in cell culture in the presence of lysing agents like sodium dodecyl sulfate (SDS) is limited by the masking effect of high levels of nonspecific fluorescence, caused by the binding of Hoe to micelles. The masking effect can be reduced substantially by increasing the concentration of the counterion, the addition of cholate, or the pH of the buffer. An optimized method was developed, combining the antimasking effects of sodium chloride, cholate, and pH to accurately determine DNA concentrations as low as 15 ng/ml in the presence of up to 6.9 mM (0.2%) SDS. The effectiveness of SDS in cell dissolution can now be combined with the specificity and sensitivity of Hoe to determine cellular DNA.

Animals↗
PubMed1990

Characterization of inside-out oriented H(+)-ATPases in cholate-pretreated renal brush-border membrane vesicles.

Exposure of porcine renal brush-border membrane vesicles to 1.2% cholate and subsequent detergent removal by dialysis reorients almost all N-ethylmaleimide (NEM)-sensitive ATPases from the vesicle inside to the outside. ATP addition to cholate-pretreated, but not to intact, vesicles causes H+ uptake as visualized by the delta pH indicator, acridine orange. The reoriented H(+)-pump is electrogenic because permeant extravesicular anions or intravesicular K+ plus valinomycin enhance H+ transport. ATP stimulates H+ uptake with an apparent Km of 93 microM. Support of H+ uptake and Pi liberation by ATP greater than GTP approximately ITP greater than UTP indicates a preference for ATP and utilization of other nucleotides at lower efficiency. ADP is a potent, competitive inhibitor of ATP-driven H+ uptake (Ki, 24 microM), Mg2+ and Mn2+ support ATP-driven H+ uptake, but Ca2+, Ba2+, and Zn2+ do not, 1 mM Zn2+ inhibits MgATP-driven H+ transport completely. NEM-sensitive Pi liberation is stimulated by Mg2+ and Mg2+ and, unlike H+ uptake, also by Ca2+ suggesting Ca2(+)-dependent ATP hydrolysis unrelated to H+ transport. The inside-out oriented H(+)-pump is relatively insensitive toward oligomycin, azide, N,N'-dicyclohexylcarbodiimide (DCCD) and vanadate, but efficiently inhibited by NEM (apparent Ki, 0.77 microM), and 4-chloro-7-nitro-benzoxa-1,3-diazole (NBD-Cl; apparent Ki, 0.39 microM). Taken together, the H(+)-ATPase of proximal tubular brush-border membranes exhibits characteristics very similar to those of "vacuolar type" (V-type) H(+)-ATPases. Hence, V-type H(+)-ATPases occur not only in intracellular organelles but also in specialized plasma membrane areas.

Acridine Orange↗
PubMed1989

Cholate effects on all-trans-retinyl palmitate hydrolysis in tissue homogenates: solubilization of multiple kidney membrane hydrolases.

Retinyl ester hydrolysis was observed in the absence of cholate in homogenates of rat lung, liver, kidney, intestine, and testes. Eighty-four percent of the activity in kidney was membrane-associated. The kidney microsomal fraction contained 19% of the total activity and was the only subcellular fraction that had increased specific activity relative to the homogenate (about 1.5-fold). In contrast, the cytosol was the only fraction that was decreased in specific activity (about 3-fold). Cholate (18 mM), reportedly required to observe hydrolysis of all-trans-retinyl esters by rat liver preparations, was not obligatory for activity in kidney homogenates or microsomes. The microsomal activity was solubilized efficiently and with a twofold increase in specific activity by the synthetic detergent 1-S-octyl-beta-D-thioglucopyranoside. Gel-permeation chromatography of the solubilizate suggested that at least two pools of activity existed, with molecular weights in the ranges 70-95 and 30-40 kDa. Neither hydrolyzed cholesteryl oleate. Both were more active in hydrolyzing retinyl palmitate than trioleoylglycerol. The higher mass pool had decreased trioleoylglycerol hydrolase activity relative to the solubilizate. Anion-exchange chromatography separated the lower mass pool into two major peaks. A major peak, distinct from the two peaks observed with the lower mass pool, was observed upon anion-exchange chromatography of the higher mass pool. These data demonstrate that multiple retinyl ester hydrolases, more efficient at hydrolyzing retinyl esters than cholesteryl esters and triacylglycerol, occur in a retinoid target tissue.

Animals↗
PubMed1992

Cholate solubilization of liver microsomal membrane components which promote NADPH-supported lipid peroxidation.

NADPH-supported lipid peroxidation monitored by malondialdehyde (MDA) production in the presence of ferric pyrophosphate in liver microsomes was inactivated by heat treatment or by trypsin and the activity was not restored by the addition of purified NADPH-cytochrome P450 reductase (FPT). The activity was differentially solubilized by sodium cholate from microsomes, and the fraction solubilized between 0.4 and 1.2% sodium cholate was applied to a Sephadex G-150 column and subfractionated into three pools, A, B, and C. MDA production was reconstituted by the addition of microsomal lipids and FPT to specific fractions from the column, in the presence of ferric pyrophosphate and NADPH. Pool B, after removal of endogenous FPT, was highly active in catalyzing MDA production and the disappearance of arachidonate and docosahexaenoate, and this activity was abolished by heat treatment and trypsin digestion, but not by carbon monoxide. The rate of NADPH-supported lipid peroxidation in the reconstituted system containing fractions pooled from Sephadex G-150 columns was not related to the content of cytochrome P450. p-Bromophenylacylbromide, a phospholipase A2 inhibitor, inhibited NADPH-supported lipid peroxidation in both liver microsomes and the reconstituted system, but did not block the peroxidation of microsomal lipid promoted by iron-ascorbate or ABAP systems. Another phospholipase A2 inhibitor, mepacrine, poorly inhibited both microsomal and pool-B'-promoted lipid peroxidation, but did block both iron-ascorbate-driven and ABAP-promoted lipid peroxidation. The phospholipase A2 inhibitor chlorpromazine, which can serve as a free radical quencher, blocked lipid peroxidation in all systems. The data presented are consistent with the existence of a heat-labile protein-containing factor in liver microsomes which promotes lipid peroxidation and is not FPT, cytochrome P450, or phospholipase A2.

Animals↗
PubMed1979

The isolation of bovine-heart cytochrome c oxidase subunits. Dependence on phospholipid and cholate-content.

The polypeptide chains of bovine-heart cytochrome c oxidase were preparatively isolated by a simple large-scale procedure based on gel permeation chromatography in the presence of sodium dodecyl sulphate. The resolution of the subunits as a function of the cholate and phospholipid content of the preparation was investigated. Cholate, and to a lesser extent, phospholipids interfere with the separation of the subunits; however, they do not prevent dissociation of the enzyme by SDS. Bovine-heart cytochrome c oxidase consists of six major subunits (estimated molecular weights in thousands: 40, 25, 20, 14, 12 and 10). In addition, the enzyme preparation contains at least five minor constituents, present in less than stoichiometric amounts. The first two of the three large subunits, all of which are hydrophobic, have amino-terminal N-formylmethionine. Subunit III, however, has a free methionine N-terminus.

Amino Acids↗
PubMed1976

Detergent extraction of erythrocyte ghosts. Comparison of residues after cholate and Triton X-100 treatments.

1. Human erythrocyte ghosts were extracted with individual free and conjugated bile salts and, for comparison, with Triton X-100 under conditions approximating to physiological temperature, pH and tonicity. 2. Treatment with cholate, glycocholate, taurocholate, or with Triton X-100 gave lipid-depleted residues. These could still be seen as ghost-like profiles by phase contrast microscopy. Deopxycholate brought about complete membrane dissolutiom. 3. The cholate residue gave a trilamellar image by electron microscopy and in condensed form gave a smaller membrane repeat than untreated membranes. It had a polypeptide composition representing mainly integral proteins. 4. The Triton X-100 residue had a granular profile in the electron microscope and a polypeptide composition largely representing peripheral proteins.

Bile Acids and Salts↗
PubMed1979

Exchangeability and rate of flip-flop of phosphatidylcholine in large unilamellar vesicles, cholate dialysis vesicles, and cytochrome oxidase vesicles.

Three model membrane systems have been characterized in terms of their interaction with phospholipid exchange proteins. Large unilamellar vesicles of phosphatidylcholine prepared by ether vaporization are shown to be homogeneous by gel filtration. Phospholipid exchange proteins from three sources are capable of catalyzing the rapid exchange of approximately half of the phospholipid from these vesicles. The remaining pool of radioactive phospholipid is virtually nonexchangeable (t1/2 of several days). Small unilamellar vesicles of phosphatidylcholine prepared by cholate dialysis also exhibit two pools of phospholipid (65% rapidly exchangable, 35% very slowly exchangeable) when incubated with beef liver phospholipid exchange protein. Cytochrome oxidase vesicles prepared both by a cholate dialysis method and by a direct incorporation method have been fractionated on a Ficoll discontinuous gradient, and tested for interaction with beef heart exchange protein. Two pools of phospholipid are once again observed (70% rapidly exchangable, 30% nonexchangeable), even for vesicles which have incorporated the transmembranous enzyme at a phospholipid to protein weight ratio of 2. The size of the rapidly exchangeable pool of phosphatidylcholine for each of the vesicle systems is consistent with the calculated fraction of phospholipid in the outer monolayer. The extremely slow rate of exchange of the second pool of the second pool of phospholipid reflects the virtual nonexistence of phospholipid flip-flop in any of these model membranes.

Biological Transport↗
PubMed1984

3'-Isothiocyanatobenzamido[3H]cholate, a new affinity label for hepatocellular membrane proteins responsible for the uptake of both bile acids and phalloidin.

Substitution of the hydroxyl group on C7 of cholic acid by a benzamido group leads to a derivative with inhibiting quality for the inward transport of both bile acids and phallotoxins by isolated liver cells. The tritiated isothiocyanate derivative was prepared (3'- isothiocyanatobenzamido [3H]cholate, [3H] IBCA ) with a specific activity of 70-80 mCi/mmol. The latter compound was used for affinity labeling of liver plasma membranes in order to detect chemically modified proteins involved in the transport of bile acids. [3H] IBCA and the noncovalently binding analogs were recognized by the transport system; they inhibited the uptake of both [14C]cholate and of demethyl[3H] phalloin in vitro. Isothiocyanatobenzamidocholate ( IBCA ) was able to protect isolated hepatocytes against phalloidin. In isolated and purified plasma membranes prepared from liver cells [3H] IBCA binds to saturable sites in an irreversible manner. Micromolar concentrations of unlabeled IBCA or millimolar concentrations of natural substrates prevented [3H] IBCA binding in a concentration dependent manner; some other substrates of the transport system also protected liver membranes against chemical modification. Membranes from AS- 3OD hepatoma cells, well known to transport neither bile acids nor phallotoxins, could not be labeled by [3H] IBCA . The major targets of labeling in hepatocellular plasma membranes were polypeptides with molecular mass of 67, 60, 54, 50, and 37 kDa as shown by SDS-polyacrylamide gel electrophoresis (10% acrylamide). The 67 kDa protein could be found in the aqueous phase after phase separation in Triton X-114. The 54 kDa and 50 kDa proteins remained in the detergent phase and can therefore be regarded as integral membrane proteins.

Affinity Labels↗
PubMed1989

Bile acid binding proteins in hepatocellular membranes of newborn and adult rats. Identification of transport proteins with azidobenzamidotauro[14C]cholate ([14C]ABATC).

Neonatal hepatocytes are less active in uptake of bile acids than are mature hepatocytes. This phenomenon has been further investigated by transport studies with azidobenzamidotaurocholate (ABATC). Taurocholate, cholate and the photolabile ABATC were taken up by liver cells of adult rats by a sodium-dependent and by an additional sodium-independent mechanism. In the dark, ABATC inhibited the uptake of taurocholate and cholate. Taurocholate decreased the transport of ABATC in a competitive manner, both in the presence and absence of sodium. In neonatal hepatocytes the Vmax for taurocholate and for ABATC was similar but was lower than in mature liver cells. In contrast, the Km was similar for neonatal and mature hepatocytes. For identification of binding proteins in both kinds of cells ABATC was photolysed after preincubation with isolated hepatocytes. Under our experimental conditions (single ultraviolet flash) about 80% of the azido groups was converted to nitrene. The covalently binding nitrene derivative inhibited bile salt transport irreversibly. Photolabeling of intact hepatocytes or of isolated plasma membranes with ABATC resulted in radioindication of membrane proteins with 67, 60, 54, 50 and 43 kDa in mature plasma membranes but of proteins with masses of 67, 54, 43 and 37 kDa in neonatal basolateral membranes. The 50 kDa protein in largely lacking in membranes of 9-day-old rats. The process of photolabeling itself was sodium-independent when isolated cells were treated with ABATC. In contrast, the degree of labeling of intact hepatocytes was markedly reduced in the absence of sodium and chloride. 100-fold molar excess of taurocholate, benzamidotaurocholate (BATC), phalloidin or cyclosomatostatin protected isolated plasma membranes against coupling of ABATC. Photolabeling of hepatoma cells known to be deficient in bile salt transport did not result in radiomodification of membrane proteins.

Affinity Labels↗
PubMed1984

Characterization of cholate-solubilized dopamine receptors from human, dog and rat brain.

[3H]Spiperone binding sites were solubilized in high yield from human, dog and rat brain with a mixture of sodium cholate (0.3% w/v) and sodium chloride (1.4 M). The binding sites were not sedimented after one hour at 100,000 g, they passed freely through 0.20 micron filters, migrated as a single peak in gradient sedimentation and were retarded upon gel filtration, proving that they were truly solubilized. The solubilized binding sites were definitely of dopaminergic nature. They showed saturable, reversible, high affinity binding of [3H]spiperone; displacement of [3H]spiperone binding by nanomolar concentrations of dopamine antagonists and micromolar concentrations of serotonin antagonists; stereo-specificity and a good correlation with drug affinities for membrane preparations. The non-displaceable, non-specific [3H]spiperone binding was very low. Gradient sedimentation analysis revealed a sedimentation coefficient of 12 S for dog solubilized preparations, 9 S for rat solubilized preparations and only 2.5 S for human solubilized preparations (values, uncorrected for detergent binding). Gel filtration experiments seem to confirm these molecular characteristics. Therefore the present results show that the dopamine receptor reveals the same pharmacological properties when solubilized with cholate-salt from rat, dog or human brain, while physico-chemical properties seem to indicate some differences.

Animals↗
PubMed1984

Cyclosporin A protects liver cells against phalloidin. Potent inhibition of the inward transport of cholate and phallotoxins.

Cyclosporin A at concentrations of more than 10 nM protects isolated hepatocytes against the action of phalloidin. Cyclosporin A at 100 nM inhibits the uptake of demethyl[3H]phalloin by 50%, and at 5 microM also that of [14C]cholate. This inhibition is independent of the preincubation period and is not reversed by washing the cells. With a 30-60-fold excess of cyclosporin A, affinity labeling of plasma membrane proteins using 12 microM [3H]isothiocyanatobenzamido cholate was reduced to 40-60% of the control. These findings indicate that transport inhibition by cyclosporin A in liver cells cannot be explained by simple competition on the level of the membrane protein(s) involved.

Affinity Labels↗
PubMed1986

Effect of sodium taurocholate and sodium cholate on short-circuit current on amphibian membranes.

The effects of the bile salts, sodium taurocholate (NaTc) and sodium cholate (NaCh), and toad bile gallbladder (bile) on short-circuit current (SCC) across isolated skin, and sodium taurocholate (NaTc) on isolated bladder of Bufo arenarum toads were tested. Sodium taurocholate (NaTc), sodium cholate (NaCh) and toad bile gallbladder (bile) promoted an increase in SCC, when added to the external side. The stimulatory effect was reversible after rinsing the preparation for 60 min. Implications on in vivo renal function of these results are discussed.

Animals↗
PubMed1985

Self-association of sodium cholate in isotonic saline solutions.

The self-association of dialyzed solutions of sodium cholate in isotonic saline solutions has been studied by vapor pressure osmometry and sedimentation equilibrium. These studies were carried out at 25, 31 and 37 degrees C. In all experiments the self-association could be described as a two-equilibrium constant, indefinite self-association in which odd species beyond monomer were absent. The plots of M1/Mna or M1/Mwa vs. c were quite smooth with no sharp breaks; this suggested that there were no critical phenomena. The temperature dependence of the self-association was quite small. Our results are in accord with other studies on sodium cholate which indicate that the self-association involves several species, and that it is not a monomer-n-mer self-association.

Centrifugation↗
PubMed2003

Temperature effect on solubilization of n-alkylbenzenes into sodium cholate micelles.

The solubilization of n-alkylbenzenes (benzene, toluene, ethylbenzene, n-propylbenzene, n-butylbenzene, n-pentylbenzene, n-hexylbenzene) into an aqueous micellar solution of sodium cholate was carried out. Solubilizate concentrations at equilibrium were determined spectrophotometrically at 293.2, 298.2, 303.2, 308.2, and 313.2 K. The first stepwise association constants (K(1)) between solubilizate monomers and vacant micelles were evaluated from the equilibrium concentrations and found to increase with increasing hydrophobicity of the solubilizate molecules. From the Gibbs energy change for solubilization at different micelle aggregation numbers and from the molecular structure of the solubilizates, the function of sodium cholate micelles as solubilizer was discussed. Enthalpy and entropy changes of solubilization were calculated from the temperature dependence of the K(1) values, and the solubilization was found to be enthalpy-driven for the solubilizates with shorter alkyl chains. The results obtained were also compared with those for conventional aliphatic micelles.

Journal Article↗
PubMed1991

Cholate-solubilized erythrocyte glucose transporters exist as a mixture of homodimers and homotetramers.

The molecular size of purified, human erythrocyte glucose transport protein (GLUT1) solubilized in cholic acid was determined by size-exclusion chromatography (SEC) and sucrose gradient ultracentrifugation. GLUT1 purified in the presence of dithiothreitol (GLUT1 + DTT) is resolved as a complex of average Stokes' radius 5.74 nm by SEC. This complex displays D-glucose-inhibitable cytochalasin B binding and, upon reconstitution into proteoliposomes, catalyzes cytochalasin B inhibitable D-glucose transport. GLUT1 purified in the absence of dithiothreitol (GLUT1-DTT) is resolved by SEC as at least two particles of average Stokes' radii 5.74 (minor component) and 7.48 nm (major component). Solubilization of GLUT1-DTT in the presence of dithiothreitol reduces the amount of 7.48-nm complex and increases the amount of 5.74-nm complex resolved by SEC. GLUT1-DTT displays D-glucose-inhibitable cytochalasin B binding and, upon reconstitution into proteoliposomes, catalyzes cytochalasin B inhibitable D-glucose transport. Sucrose gradient ultracentrifugation of GLUT1 + DTT in cholate resolves GLUT1 into two components of 4.8 and 7.6 S. The 4.8S complex is the major component of GLUT1 + DTT. The reverse profile is observed upon sucrose gradient ultracentrifugation of GLUT1-DTT. SEC of human erythrocyte membrane proteins resolves GLUT1 as a major broad peak of average Stokes' radius 7.48 nm and a minor component of 5.74 nm. Both components are characterized by D-glucose-inhibitable cytochalasin B binding. Purified GLUT1 is associated with approximately 26 tightly bound lipid molecules per monomer of transport protein. These data suggest that purified GLUT1 exists as a mixture of homodimers and homotetramers in cholate-lipid micelles and that the presence of reductant during solubilization favors dimer formation.

Catalysis↗