scholarly journals Concomitant stimulation by vasopressin of biliary and perfusate calcium fluxes in the perfused rat liver

1992 ◽  
Vol 281 (2) ◽  
pp. 387-392 ◽  
Author(s):  
Y Hamada ◽  
A Karjalainen ◽  
B A Setchell ◽  
J E Millard ◽  
F L Bygrave
Keyword(s):  
Oxygen Uptake ◽  
Rat Liver ◽  
Bile Flow ◽  
Bile Secretion ◽  
Perfused Rat Liver ◽  
Diseased Liver ◽  
Glucose Output ◽  
Opposing Effects ◽  
Prior Administration ◽  
Slow Onset

Changes in perfusate Ca2+ (measured with a Ca(2+)-selective electrode) and changes in bile calcium (measured by atomic absorption spectroscopy) were continuously and simultaneously monitored after infusion of (a) vasopressin, (b) glucagon and (c) both vasopressin and glucagon together to the perfused rat liver. Also monitored were perfusate glucose and oxygen concentrations and bile flow. Vasopressin induces a sharp, transient, pulse of increased bile flow and increased bile calcium within 1 min of infusion, concomitant with rapid changes in perfusate Ca2+ fluxes, glucose output and oxygen uptake. This is immediately followed by a decrease in both bile flow and bile calcium for as long as the hormone is administered. Changes induced by glucagon are a relatively slow onset of perfusate Ca2+ efflux and oxygen uptake, but rapid glucose output, and a small but significant and transient decrease in bile flow and bile calcium which, despite the continued infusion of the hormone, spontaneously and rapidly returns to normality. However, the greatest responses are observed after co-administration of both hormones. Coincident with the augmented perfusate Ca2+ fluxes (influx) seen in earlier work, there occurs within 1 min of vasopressin infusion a sharp increase in bile secretion and bile calcium greater in magnitude than that produced by vasopressin alone. Immediately thereafter bile secretion and bile calcium decline below basal values and remain there for as long as the hormones are administered. Glucagon and vasopressin therefore each have opposing effects on bile flow and bile calcium. However, the action of vasopressin is enhanced by the prior administration of glucagon. The data thus reveal features about the actions of glucagon and Ca(2+)-mobilizing hormones on bile flow and bile calcium not previously recorded and provide a novel framework around which the whole issue of hepato-biliary Ca2+ homoeostasis can be assessed in normal and diseased liver.

Endothelin-1 stimulates bile acid secretion and vesicular transport in the isolated perfused rat liver

1994 ◽  
Vol 266 (2) ◽  
pp. G324-G329 ◽  
Author(s):  
A. Tanaka ◽  
K. Katagiri ◽  
M. Hoshino ◽  
T. Hayakawa ◽  
K. Tsukada ◽  
...  
Keyword(s):  
Bile Acid ◽  
Rat Liver ◽  
Bile Flow ◽  
Low Dose ◽  
Portal Pressure ◽  
Vesicular Transport ◽  
Bile Secretion ◽  
Isolated Perfused Rat Liver ◽  
High Dose ◽  
Perfused Rat Liver

The effects of endothelin (ET) on portal pressure and bile secretion were examined using isolated perfused rat liver and rat hepatocyte preparations. ET-1 raised portal pressure dose dependently; administration at a high dose (10(-9) mol) induced a > 200% increase along with reduced bile flow and decreased secretion of bile acid and phospholipids. However, a low dose (10(-10) mol) of ET-1 brought about a < 100% portal pressure rise, enhanced both bile flow and excretion of bile acid and phospholipids, and significantly increased transfer of preadministered horseradish peroxidase (HRP) into bile. In addition, values for Ca2+ concentrations, examined by indo 1 fluorescence, were elevated in isolated hepatocytes after administration of ET-1. Papaverine suppressed the low-dose ET-1 stimulation effects on both portal pressure and bile secretion. Moreover, it also reduced the HRP excretion and suppressed intracellular Ca2+ release. This study demonstrated that ET-1 stimulates vesicular transport, probably via promotion of intracellular Ca2+ release, and, as a result, increases bile acid-dependent bile flow.

Stimulation of oxygen uptake by prostaglandin E2 is oxygen dependent in perfused rat liver

1998 ◽  
Vol 275 (3) ◽  
pp. G542-G549 ◽  
Author(s):  
Wei Qu ◽  
Zhi Zhong ◽  
Gavin E. Arteel ◽  
Ronald G. Thurman
Keyword(s):  
Oxygen Uptake ◽  
Oxygen Tension ◽  
Rat Liver ◽  
Kupffer Cells ◽  
High Flow ◽  
Perfused Rat Liver ◽  
Normal Flow ◽  
Flow Rates ◽  
Glucose Output ◽  
Parenchymal Cells

The aim of this study was to determine if the effect of prostaglandin E2(PGE2) on hepatic oxygen uptake was affected by oxygen tension. Livers from fed female Sprague-Dawley rats were perfused at normal or high flow rates (4 or 8 ml ⋅ g−1 ⋅ min−1) to vary local oxygen tension within the liver lobule. During perfusion at normal flow rates, PGE2 (5 μM) infusion increased oxygen uptake by about 50 μmol ⋅ g−1 ⋅ h−1; however, when livers were perfused at high flow rates, the increase was nearly twice as large. Simultaneously, glucose output was increased rapidly by about 50%, whereas glycolysis was decreased about 60%. When flow rate was held constant, increases in oxygen uptake due to PGE2 were proportional to oxygen delivery. Infusion of PGE2 into livers perfused at normal flow rates increased state 3 rates of oxygen uptake of subsequently isolated mitochondria by about 25%; however, rates were increased 50–75% in mitochondria isolated from livers perfused at high flow rates. Thus it is concluded that PGE2stimulates oxygen uptake via mechanisms regulated by oxygen tension in perfused rat liver. High flow rates also increased basal rates of oxygen uptake: this increase was prevented by inactivation of Kupffer cells with GdCl3. In addition, conditioned medium from Kupffer cells incubated at high oxygen tension (75% oxygen) stimulated oxygen uptake of isolated parenchymal cells by >30% and elevated PGE2production about twofold compared with Kupffer cells exposed to normal air-saturated buffer (21% oxygen). These effects were blocked completely by both indomethacin and nisoldipine. These data support the hypothesis that oxygen stimulates Kupffer cells to release mediators such as PGE2 which elevate oxygen consumption in parenchymal cells, possibly by mechanisms involving cyclooxygenase and calcium channels.

scholarly journals The synergistic action (cross-talk) of glucagon and vasopressin induces early bile flow and plasma-membrane calcium fluxes in the perfused rat liver

1994 ◽  
Vol 301 (1) ◽  
pp. 187-192 ◽  
Author(s):  
A Karjalainen ◽  
F L Bygrave
Keyword(s):  
Plasma Membrane ◽  
Oxygen Uptake ◽  
Rat Liver ◽  
Bile Flow ◽  
Concomitant Administration ◽  
Synergistic Action ◽  
Perfused Rat Liver ◽  
Maximal Rate ◽  
Adrenergic Agonist ◽  
Lower Magnitude

A study was made of the initial responses of perfusate Ca2+ fluxes and bile flow to Ca(2+)-mobilizing agonists, following refinements to the methods for analysing these parameters in the perfused rat liver. Net Ca2+ efflux induced by vasopressin commences at 15 s, reaches a maximal rate at 35 s and declines to zero by 55 s, when Ca2+ influx commences. Vasopressin-induced increases in bile flow commence by 20 s, attain a maximal rate by 35 s and begin to decline at 50 s, to reach basal values by 90 s. Concomitant administration of glucagon modifies each of these actions of vasopressin in the following ways: it decreases by 5 s the time of onset of net Ca2+ efflux, and the time and magnitude of such efflux, and the time of onset of bile flow is decreased to 15 s, and the flow reaches maximal rates by 30 s. When the alpha 1-adrenergic agonist phenylephrine is used in place of vasopressin, Ca2+ efflux commences at 17-18 s and is greater in magnitude; little bile flow is induced by this agonist. Glucagon modifies the action of phenylephrine in the following ways: the onset of Ca2+ efflux is brought forward by 2-3 s, it is of lower magnitude and Ca2+ influx begins by 45 s; bile flow commences by 15-20 s, and reaches a maximum at 30 s, where the rate is much greater than in the absence of glucagon; this rate gradually declines to be near basal by 80 s. The onset of agonist-induced oxygen uptake was also brought forward by the co-administration of glucagon. Comparison of agonist-induced plasma-membrane Ca2+ fluxes and bile flow (with or without glucagon administration) suggests that correlations can be made between net Ca2+ fluxes and the transient increases seen in bile flow.

Studies on bile secretion with the aid of the isolated perfused rat liver I. Inhibitory action of sporidesmin and icterogenin

1974 ◽  
Vol 186 (1085) ◽  
pp. 333-356 ◽  
Keyword(s):  
Rat Liver ◽  
Electron Micrographs ◽  
Bile Flow ◽  
Bile Secretion ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Morphological Examination ◽  
Buffer Solution ◽  
Canalicular Membrane ◽  
Pyruvate Ratio

An isolated perfused rat liver preparation has been developed to aid the study of the mechanisms underlying the secretion of bile and the cholestatic actions of two naturally occurring agents, icterogenin and sporidesmin. The perfused liver produced bile for 3-5 h at a steady rate slightly above that observed in intact rats possessing external biliary cannulae. During this period of perfusion detailed biochemical and physiological studies on the behaviour of the liver were carried out. Morphological examination of the livers after several hours of perfusion was performed by means of electron microscopy and quantitative analysis of the pictures for certain structural elements has been performed. The addition of ethanol (final concentration 27 mM) to control perfusion had no significant effect on bile flow or liver morphology except that there was a decrease in the numbers of multi- and mono-vesicular bodies and in their relative proportions in the cytoplasm. There was a large though transient increase in perfusate lactate to pyruvate ratio and a sharp fall in the perfusate pH. Sporidesmin (2 mg in ethanol-buffer solution) rapidly decreased bile flow, and retarded the increase in the lactate to pyruvate ratio and the decrease in the pH of the perfusate seen in ethanol controls. Electron micrographs of the livers following sporidesmin administration showed large regions of the bile canaliculi devoid of microvilli and there was the appearance in the cytoplasm of lysosomal-like structures containing numerous glycogen granules. Icterogenin (4 mg in ethanol-buffer solution) produced a rapid cholestasis, inhibited the changes in the lactate to pyruvate ratio and the perfusate pH seen in the ethanol control preparations. Electron micrographs of the icterogenin-treated livers revealed changes in the canalicular membrane, extrusion of material into the canalicular lumen and aggregation of lysosomes in the cytoplasm. These studies suggest that bile flow in the rat is seriously affected by disturbances to the canalicular membrane, and preliminary biochemical investigations of these disturbances are reported here.

Vanadate inhibits glucose output from isolated perfused rat liver

Hepatology ◽  
1991 ◽  
Vol 14 (3) ◽  
pp. 540-544 ◽  
Author(s):  
Rafael Bruck ◽  
Haia Prigozin ◽  
Zipora Krepel ◽  
Paul Rotenberg ◽  
Yoram Shechter ◽  
...  
Keyword(s):  
Rat Liver ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Glucose Output

Effect of bile salts on bile flow and membrane associated Na-K-ATPase in the perfused rat liver

1995 ◽  
Vol 108 (4) ◽  
pp. A1205
Author(s):  
T. You ◽  
S. Güldütuna ◽  
S. Bhatti ◽  
U. Leuschner
Keyword(s):  
Rat Liver ◽  
Bile Flow ◽  
Bile Salts ◽  
Perfused Rat Liver

Nifedipine modulation of biliary GSH and GSSG/ conjugate efflux in normal and regenerating rat liver

2001 ◽  
Vol 281 (1) ◽  
pp. G85-G94 ◽  
Author(s):  
Bo Yang ◽  
Ceredwyn E. Hill
Keyword(s):  
Bile Acid ◽  
Sodium Nitroprusside ◽  
Rat Liver ◽  
Driving Force ◽  
Bile Flow ◽  
Organic Anion ◽  
High Capacity ◽  
Perfused Rat Liver ◽  
High Affinity ◽  
Glutathione Conjugate Transport

Canalicular glutathione secretion provides the major driving force for bile acid-independent bile flow (BAIF), although the pathways involved are not established. The hypothesis that GSH efflux proceeds by a route functionally distinct from the high-affinity, low-capacity, mrp2-mediated pathway was tested by using perfused rat liver and three choleretic compounds that modify biliary secretion of GSH (the dihydropyridine nifedipine and organic anion probenecid) or GSSG [sodium nitroprusside (SNP)]. Whereas nifedipine (30 μM) stimulated GSH secretion and blocked SNP-stimulated GSSG efflux and choleresis, SNP (1 mM) was ineffective against nifedipine-stimulated GSH efflux or BAIF, suggesting that most GSSG exits through a GSH-inhibitable path independent of high-affinity GSSG/glutathione conjugate transport. Three observations support this proposal. SNP, but not nifedipine, significantly inhibited bromosulfophthalein (BSP, 1 μM) excretion. Probenecid (1 mM) blocked resting or nifedipine-stimulated GSH secretion but only weakly inhibited BSP excretion. Glutathione, but not BSP, efflux capacity was reduced following partial hepatectomy. We suggest GSH efflux is mediated by a high-capacity organic anion pathway capable of GSSG transport when its high-affinity route is saturated.

Coordinated regulation of hepatic glycogen formation in perfused rat liver by glucose and lactate

1994 ◽  
Vol 266 (4) ◽  
pp. E583-E591 ◽  
Author(s):  
Z. Zhang ◽  
J. Radziuk
Keyword(s):  
Rat Liver ◽  
Dose Response ◽  
Glycogen Synthesis ◽  
Hepatic Glycogen ◽  
Perfused Rat Liver ◽  
Response Curves ◽  
Liver Preparation ◽  
Lactate Uptake ◽  
Glucose Output ◽  
Glycogen Formation

Lactate has been found to enhance the formation of glycogen from both glucose and lactate as substrate (Z. Zhang and J. Radziuk. Biochem. J. 280: 415–419, 1991). To evaluate the relative importance of its role as substrate and regulatory factor, a dual dose-response evaluation was done by adding variable amounts of glucose and lactate to the medium in a recirculating perfused rat liver preparation. Nine groups of perfusions were performed utilizing three different levels of carbon infusion into the system: 0.25, 1.0, and 2.0 mg/min. These levels of carbon infusion were further subdivided into different relative amounts of glucose and lactate. Lactate uptake by the perfused liver was linearly related with net glucose output, regardless of the glucose concentrations. In contrast to this, the effect of lactate uptake on the rate of glycogen synthesis is saturable. Moreover, the rate of glycogen formation at which this saturation occurs is dependent only on the mean perfusate glucose concentration. The highest amount of glycogen formed in a 2-h period was 50 +/- 7 mg and the lowest 3.4 +/- 0.3 mg. A family of dose-response curves was generated describing this dual dependence of glycogen formation (both direct and gluconeogenetic pathways) on lactate and glucose.

scholarly journals Changes in oxygen consumption induced by t-butyl hydroperoxide in perfused rat liver. Effect of free-radical scavengers

1984 ◽  
Vol 223 (3) ◽  
pp. 879-883 ◽  
Author(s):  
L A Videla ◽  
M I Villena ◽  
G Donoso ◽  
C Giulivi ◽  
A Boveris
Keyword(s):  
Oxygen Consumption ◽  
Free Radical ◽  
Oxygen Uptake ◽  
Rat Liver ◽  
Recovery Phase ◽  
Free Radical Scavengers ◽  
Perfused Rat Liver ◽  
Radical Scavengers ◽  
Butyl Hydroperoxide ◽  
Biphasic Effect

The addition of t-butyl hydroperoxide to perfused rat liver elicited a biphasic effect on hepatic respiration. A rapid fall in liver oxygen consumption was initially observed, followed by a recovery phase leading to respiratory rates higher than the initial steady-state values of oxygen uptake. This overshoot in hepatic oxygen uptake was abolished by free-radical scavengers such as (+)-cyanidanol-3 or butylated hydroxyanisole at concentrations that did not alter mitochondrial respiration. (+)-Cyanidanol-3 was also able to facilitate the recovery of respiration, the diminution in the calculated rate of hydroperoxide utilization and the decrease in liver GSH content produced by two consecutive pulses of t-butyl hydroperoxide. It is suggested that the t-butyl hydroperoxide-induced overshoot in liver respiration is related to increased utilization of oxygen for lipid peroxidation as a consequence of free radicals produced in the scission of the hydroperoxide by cellular haemoproteins.

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