A novel transcellular transport pathway for non-bile salt cholephilic organic anions

1991 ◽  
Vol 261 (2) ◽  
pp. G305-G311 ◽  
Author(s):  
N. Aoyama ◽  
H. Tokumo ◽  
T. Ohya ◽  
K. Chandler ◽  
R. T. Holzbach
Keyword(s):  
Bile Salt ◽  
Inhibitory Effect ◽  
Organic Anions ◽  
Isolated Perfused Rat Liver ◽  
Phenol Red ◽  
Transport Pathway ◽  
Single Class ◽  
Transcellular Transport ◽  
Tracer Dose ◽  
Saturation Dose

Non-bile salt cholephilic organic anions comprise a single class of nonhomologous ligands having a range of hydrophobicity. Hydrophobicity enhances the hepatic extraction of cholephiles as well as their partitioning into secreted biliary lipid particles. When hydrophobicity is correlated with patterns of biliary excretion for studying transcellular transport, however, the more hydrophobic probes are unsuitable. Specifically, with the isolated perfused rat liver technique, the excretory times for sulfobromophthalein and rose bengal were significantly longer compared with that for the much more hydrophilic analogue phenol red (PR), which showed only a single, nearly symmetrical excretory peak at 10 min. Colchicine affected the apparently well-defined PR pathway only at a saturation dose (10,000 times the tracer dose). In contrast, the effect of a different perturbant, monensin, was striking at a tracer dose of PR, but was less evident at a saturation dose. The combined administration of colchicine and monensin had no additive inhibitory effect on PR excretion at tracer doses. At a saturation dose of PR, where monensin is less inhibiting, however, a significant additive inhibitory effect was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Transcellular transport of organic anions in the isolated perfused rat liver: The differential effects of monensin and colchicine

Hepatology ◽  
1991 ◽  
Vol 14 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Nankei Aoyama ◽  
Toshihide Ohya ◽  
Kimberly Chandler ◽  
Susan Gresky ◽  
R. Thomas Holzbach
Keyword(s):  
Rat Liver ◽  
Organic Anions ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Transcellular Transport ◽  
Differential Effects

scholarly journals Effects of organic anions on biliary lipid secretion in rats. Importance of association with biliary lipid structures

1992 ◽  
Vol 286 (1) ◽  
pp. 193-196 ◽  
Author(s):  
G Yamashita ◽  
S Tazuma ◽  
G Kajiyama
Keyword(s):  
Bile Salt ◽  
Organic Anion ◽  
Sodium Taurocholate ◽  
Organic Anions ◽  
Phenol Red ◽  
Dependent Manner ◽  
Biliary Lipid ◽  
Lipid Secretion ◽  
Biliary Lipids ◽  
Salt Secretion

This study was performed to determine the effects of various organic anions on biliary lipid secretion in rats. We infused bile-salt-pool-depleted rats with sodium taurocholate at a constant rate, with or without various organic anions: Indocyanine Green (ICG), bromosulphophthalein (BSP), BSP-glutathione and Phenol Red (PR). BSP decreased biliary secretion of cholesterol and phospholipids in a dose-dependent manner without affecting bile salt secretion (uncoupling), and this change was fully reversible. In contrast, ICG, BSP-glutathione and PR did not cause such an uncoupling of biliary lipids. In addition, the distribution pattern of each organic anion to various lipid particles was determined by gel-permeation chromatography. BSP was predominantly associated with bile salt micelles, whereas vesicular association was dominant for ICG, and both BSP-glutathione and PR formed only self-aggregations. From these data, we concluded that the uncoupling of biliary lipids from bile salt secretion by BSP resulted from the interaction between BSP and bile salt micelles in the bile canaliculus, and that this interaction inhibited the capacity of bile salts to induce the secretion of phospholipids and cholesterol.

Characterization of Thromboxane A2/Prostaglandin H2 Receptors in Porcine Coronary Artery -The Inhibitory Effect of a Novel Dibenzoxepin Derivative, KW-3635

1992 ◽  
Vol 67 (05) ◽  
pp. 582-584 ◽  
Author(s):  
Ichiro Miki ◽  
Akio Ishii
Keyword(s):  
Coronary Artery ◽  
Binding Sites ◽  
Thromboxane A2 ◽  
Inhibitory Effect ◽  
Scatchard Analysis ◽  
Single Class ◽  
Porcine Coronary Artery ◽  
Equilibrium Binding ◽  
H2 Receptors

SummaryWe characterized the thromboxane A2/prostaglandin H2 receptors in porcine coronary artery. The binding of [3H]SQ 29,548, a thromboxane A2 antagonist, to coronary arterial membranes was saturable and displaceable. Scatchard analysis of equilibrium binding showed a single class of high affinity binding sites with a dissociation constant of 18.5 ±1.0 nM and the maximum binding of 80.7 ± 5.2 fmol/mg protein. [3H]SQ 29,548 binding was concentration-dependently inhibited by thromboxane A2 antagonists such as SQ 29,548, BM13505 and BM13177 or the thromboxane A2 agonists such as U46619 and U44069. KW-3635, a novel dibenzoxepin derivative, concentration-dependently inhibited the [3H]SQ 29,548 binding to thromboxane A2/prosta-glandin H2 receptors in coronary artery with an inhibition constant of 6.0 ± 0.69 nM (mean ± S.E.M.).

K+ transport across the lamprey erythrocyte membrane: characteristics of a Ba(2+)- and amiloride-sensitive pathway

1991 ◽  
Vol 159 (1) ◽  
pp. 303-324 ◽  
Author(s):  
K. Kirk
Keyword(s):  
Membrane Potential ◽  
Erythrocyte Membrane ◽  
Inhibitory Effect ◽  
Extracellular Ph ◽  
Transport Pathway ◽  
Full Effect ◽  
River Lamprey ◽  
K Concentration ◽  
86Rb Influx ◽  
K Transport

The characteristics of K+ transport in erythrocytes from the river lamprey (Lampetra fluviatilis) were investigated using standard radioisotope flux techniques. The cells were shown to have a ouabain-sensitive transport pathway that carried 43K+ and 86Rb+ into the cell at similar rates. Most of the ouabain-resistant 43K+ and 86Rb+ influx was via a pathway that was insensitive to cotransport inhibitors and to the replacement of extracellular Cl- or Na+. This pathway showed a strong selectivity for 43K+ over 86Rb+. It was inhibited fully by Ba2+ (I50 approximately 2.8 mumol l-1), amiloride (I50 approximately 150 mumol l-1) and ethylisopropylamiloride (I50 approximately 3.3 mumol l-1) and less effectively by quinine and by the tetraethylammonium ion. Inhibition by Ba2+ took full effect within a few minutes whereas the full inhibitory effect of amiloride took more than 1 h to develop. Experiments with the membrane potential probe [14C]tetraphenylphosphonium ion gave results consistent with the lamprey erythrocyte membrane having a Ba(2+)-sensitive K+ conductance that was significantly greater than the membrane Na+ conductance and which gave rise to a marked dependence of the membrane potential on the extracellular K+ concentration. The rate constants for Ba(2+)-sensitive 43K+ and 86Rb+ influx decreased (proportionally) with increasing extracellular K+ concentration in a manner that was consistent with the transport being via a conductive pathway. The decrease was attributed to a depolarisation of the membrane (in response to the increasing extracellular K+ concentration) and a consequent decrease in the driving force for the conductive movement of 43K+ and 86Rb+ into the cells. Ba(2+)-sensitive 86Rb+ influx increased significantly with decreasing cell volume and with increasing intracellular pH (at a constant extracellular pH) but increased only slightly with increasing extracellular pH. The pathway operated normally in the complete absence of extracellular Ca2+ but its activity decreased in cells pretreated with ionomycin and EGTA; this suggests a role for intracellular Ca2+ in the operation of the pathway.

scholarly journals Membrane Permeabilities of Ascorbic Acid and Ascorbate

Biomolecules ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 73 ◽  
Author(s):  
Christof Hannesschlaeger ◽  
Peter Pohl
Keyword(s):  
Ascorbic Acid ◽  
Acetic Acid ◽  
Lipid Bilayers ◽  
Redox Balance ◽  
The Other ◽  
Lipid Matrix ◽  
Transport Pathway ◽  
Transcellular Transport ◽  
Membrane Permeabilities ◽  
Ph Microelectrodes

Vitamin C (VC)—a collective term for the different oxidation and protonation forms of ascorbic acid (AscH)—is an essential micronutrient that serves as (i) a potent antioxidant and (ii) a cofactor of a manifold of enzymatic processes. Its role in health is related to redox balance maintenance, which is altered in diseases such as obesity, cancer, neurodegenerative diseases, hypertension, and autoimmune diseases. Despite its importance, VC uptake has been poorly investigated. Available literature values for the passive membrane permeability P of lipid bilayers for AscH scatter by about 10 orders of magnitude. Here, we show by voltage clamp that P − of AscH’s anionic form (ascorbate Asc − ) is negligible. To cross the membrane, Asc − picks up a proton in the membrane vicinity and releases it on the other side of the membrane. This leads to a near-membrane pH drop that was visualized by scanning pH microelectrodes. The AscH concentration dependent pH profiles indicated P   =   1.1   ±   0.1   ×   10 − 8   cm / s . Thus, AscH’s P is comparable to that of sorbitol and much lower than that of other weak acids like acetic acid or salicylic acid. The observation suggests that the capacity of the passive transcellular transport pathway across the lipid matrix does not suffice to ensure the required VC intake from the gastrointestinal tract.

Inhibitory effect of ileal oleate on postprandial motility of the upper gut

1991 ◽  
Vol 261 (3) ◽  
pp. G458-G463 ◽  
Author(s):  
Z. Dreznik ◽  
D. Brocksmith ◽  
T. A. Meininger ◽  
N. J. Soper
Keyword(s):  
Oleic Acid ◽  
Gastric Emptying ◽  
Gamma Camera ◽  
Delayed Gastric Emptying ◽  
Early Period ◽  
Inhibitory Effect ◽  
Myoelectric Activity ◽  
Phenol Red ◽  
Mixed Meal ◽  
Postprandial Motility

To determine the effect of ileal oleate on postprandial gastrointestinal motility, duodenal and paired perfusion-aspiration ileal catheters and bipolar duodenal and jejunal electrodes were surgically implanted in five dogs. The ileum was perfused with either saline or an isotonic oleic acid emulsion at 2 ml/min. A 205-kcal mixed meal containing 120 ml liquid nutrient labeled with 111In-diethylenetriamine pentaacetic acid (DTPA) and solid food labeled with 99mTc was then administered orally. Gastric emptying was assessed by a gamma camera, myoelectric activity was continuously monitored, and duodenal-ileal transit of phenol red was determined over the ensuing 240 min. Ileal oleate reduced duodenal spikeburst frequency by 50% (P less than 0.05) and delayed gastric emptying of liquids and solids. Four hours after ingesting the meal, 62% of solids and 34% of liquids were retained in the stomach during oleic acid perfusion compared with 25 and 4%, respectively, when saline was perfused (P less than 0.05). Duodenal-ileal transit was markedly slowed by ileal perfusion with the oleic acid emulsion (P less than 0.001). Ileal oleate therefore exerted a profound inhibitory effect on proximal gut motility in the early period after ingestion of a mixed-nutrient meal in dogs.

Phenol red inhibits growth of renal epithelial cells

1992 ◽  
Vol 262 (4) ◽  
pp. F687-F691 ◽  
Author(s):  
M. M. Walsh-Reitz ◽  
F. G. Toback
Keyword(s):  
Growth Factor ◽  
Cell Growth ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Calf Serum ◽  
Inhibitory Effect ◽  
Phenol Red ◽  
Mitogenic Effect ◽  
Growth Inhibitory Effect ◽  
Growth Inhibitory

Phenol red coeluted with a novel kidney cell growth factor during its isolation from conditioned medium by high-performance liquid chromatography. The possibility that phenol red rather than the putative factor mediated the growth-promoting activity was tested, because this pH indicator is known to possess estrogenic properties including a mitogenic effect. Unexpectedly, phenol red at the concentration found in Dulbecco's modified Eagle's medium (DMEM) inhibited growth of monkey (BSC-1) and canine kidney (MDCK) epithelial cells by 20-30%, but stimulated multiplication of 3T3 fibroblasts. The growth-inhibitory effect of phenol red for BSC-1 cells was reversible, concentration dependent, and cell-density independent when multiplication was examined in the presence and absence of the dye. Phenol red partially masked the mitogenic effect of calf serum and epidermal growth factor and was additive to the growth-inhibitory effect of transforming growth factor-beta 2. These observations indicate that phenol red at the concentration in DMEM both underestimates the potency of mitogens and overestimates the strength of an inhibitor of kidney epithelial cell growth and suggest that the dye be omitted from the culture medium when a new growth-regulatory compound is under study.

Intestinal and hepatic transport of cholate and organic dyes

1964 ◽  
Vol 206 (1) ◽  
pp. 239-242 ◽  
Author(s):  
C. S. Tidball
Keyword(s):  
Portal Vein ◽  
Bile Salt ◽  
Transport Mechanism ◽  
Organic Dyes ◽  
Salt Transport ◽  
Distal Ileum ◽  
Proximal Jejunum ◽  
Phenol Red ◽  
Sodium Pentobarbital ◽  
Hepatic Transport

The 3-hr cumulative biliary appearance of a bile salt and three representative organic dyes was studied in rats anesthetized with sodium pentobarbital. The substances were administered in one of the following locations: a branch of the portal vein, a 20-cm isolated loop of proximal jejunum, or a similar loop of distal ileum. Average biliary recoveries of 10 mg cholate, bromsulfonphthalein, diiodotetrachlorofluorescein (rose bengal) or phenolsulfonphthalein (phenol red) introduced slowly into the portal circulation were 97, 97, 68, and 23%, respectively. The respective recoveries of 30-mg quantities of these four substances placed in the intestinal loops were 43, 5, 2, and 1% proximally and 90, 5, 5, and 0.4% distally. These observations confirm the presence of a specific intestinal transport mechanism for cholate with maximal activity in the distal ileum. However, the three representative organic dyes are shown not to be carried by the intestinal bile salt transport mechanism and their movement from gut lumen to portal vein blood should be ascribed to a passive process.

Osmoltye and tryptophan receptors controlling gastric emptying in the dog

1976 ◽  
Vol 231 (3) ◽  
pp. 848-853 ◽  
Author(s):  
Stephens ◽  
RF Woolson ◽  
AR Cooke
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Gastric Emptying ◽  
Brush Border ◽  
Inhibitory Effect ◽  
Intestinal Cell ◽  
Acid Transport ◽  
Transport Pathway ◽  
Molar Basis ◽  
Intestinal Receptors

The effect of three monosaccharides, three disaccharides, two dipeptides, combinations of tryptophan with two hexoses, one hexitol, and two amino acids ongastric emptying was studied in dogs to further define the samll intestinal receptors responsive to osmolytes and tryptophan. On a molar basis the disacchardies and dipeptides were almost twice as potent as their respective constituent monosaccharides or amino acids implying that the osmoreceptor is deep to the brush border disaccharidases and cytosol dipeptidases. Tryptophan probably acts by a mechanism different from the osmoreceptor since slowing of gastric emptying by tryptophan was inhibited by methionine which has no effect on a stimulant of the osmoreceptor mechanism. Lysine unlike methionine does not share the neutral amino acid transport pathway with tryptophan. Lysine did not change the inhibitory effect of tryptophan on gastric emptying. This imples that transport of tryptophan into the intestinal cell is necessary for its slowing effect. Glucose and galactose also inhibited the tryptophan effect whereas a nonabsorbed hexitor, mannitol, was without effect. Interference by the hexoses was also probably by competition with tryptophan for transport into the cell. These studies further indicate that the tryptophan receptor is different from the osmoreceptor.

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