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.

scholarly journals The Ca2+-mobilizing actions of vasopressin and angiotensin differ from those of the α-adrenergic agonist phenylephrine in the perfused rat liver

1985 ◽  
Vol 232 (3) ◽  
pp. 911-917 ◽  
Author(s):  
J G Altin ◽  
F L Bygrave
Keyword(s):  
Plasma Membrane ◽  
Rat Liver ◽  
Similar Amount ◽  
Perfused Rat Liver ◽  
Adrenergic Agonists ◽  
Adrenergic Agonist ◽  
Hormone Administration ◽  
Sensitive Electrode ◽  
Stimulation Of

A Ca2+-sensitive electrode was used to study net Ca2+-flux changes induced by the administration of phenylephrine, vasopressin and angiotensin to the perfused rat liver. The studies reveal that, although the Ca2+ responses induced by vasopressin and angiotensin are similar, they are quite different from the Ca2+ fluxes induced by phenylephrine. The administration of phenylephrine is accompanied by a stimulation of a net amount of Ca2+ efflux (140 nmol/g of liver). A re-uptake of a similar amount of Ca2+ occurs only after the hormone is removed. In contrast, the administration of vasopressin or angiotensin to livers perfused with 1.3 mM-Ca2+ induces the release of a relatively small amount of Ca2+ (approx. 40 nmol/g of liver) during the first 60 s. This is followed by a much larger amount of Ca2+ uptake (70-140 nmol/g of liver) after 1-2.5 min of hormone administration, and a slow efflux or loss of a similar amount of Ca2+ over a period of 6-8 min. At lower concentrations of perfusate Ca2+ (less than 600 microM) these hormones induce only a net efflux of the ion. These results suggest that at physiological concentrations of extracellular Ca2+ the mechanism by which alpha-adrenergic agonists mobilize cellular Ca2+ is different from that involving vasopressin and angiotensin. It seems that the hormones may have quite diverse effects on Ca2+ transport across the plasma membrane and perhaps organellar membranes in liver.

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.

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.

scholarly journals Phosphatidic acid and arachidonic acid each interact synergistically with glucagon to stimulate Ca2+ influx in the perfused rat liver

1987 ◽  
Vol 247 (3) ◽  
pp. 613-619 ◽  
Author(s):  
J G Altin ◽  
F L Bygrave
Keyword(s):  
Arachidonic Acid ◽  
Phosphatidic Acid ◽  
Synergistic Action ◽  
Perfused Rat Liver ◽  
O2 Uptake ◽  
Adrenergic Agonist ◽  
Glucose Output ◽  
Rat Livers ◽  
Alpha Adrenergic Agonist ◽  
Stimulation Of

The administration of phosphatidic acid to rat livers perfused with media containing either 1.3 mM- or 10 microM-Ca2+ was followed by a stimulation of Ca2+ efflux, O2 uptake and glucose output. The responses elicited by 100 microM-phosphatidic acid were similar to those induced by the alpha-adrenergic agonist phenylephrine. Contrary to suggestions that phosphatidic acid acts like a Ca2+-ionophore, no net influx of Ca2+ was detected until the phosphatidic acid was removed. Sequential infusions of phenylephrine and phosphatidic acid indicate that the two agents release Ca2+ from the same intracellular source. The co-administration of glucagon (or cyclic AMP) and phosphatidic acid, and also of glucagon and arachidonic acid, led to a synergistic stimulation of Ca2+ uptake of the liver, a feature similar to that observed after the co-administration of glucagon and other Ca2+-mobilizing hormones [Altin & Bygrave (1986) Biochem. J. 238, 653-661]. A notable difference, however, is that the synergistic stimulation of Ca2+ uptake induced by the co-administration of glucagon and arachidonic acid was inhibited by indomethacin, whereas that induced by glucagon and phosphatidic acid, or glucagon and other Ca2+-mobilizing agents, was not. The results suggest that the synergistic action of glucagon and arachidonic acid in stimulating Ca2+ influx is mediated by prostanoids, but that of glucagon and phosphatidic acid is evoked by a mechanism similar to that of Ca2+-mobilizing agents.

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.

scholarly journals Acute effects of cholestatic and choleretic bile salts on vasopressin- and glucagon-induced hepato-biliary calcium fluxes in the perfused rat liver

1992 ◽  
Vol 283 (2) ◽  
pp. 575-581 ◽  
Author(s):  
Y Hamada ◽  
A Karjalainen ◽  
B A Setchell ◽  
J E Millard ◽  
F L Bygrave
Keyword(s):  
Bile Salt ◽  
Rat Liver ◽  
Strong Correlation ◽  
Bile Flow ◽  
Bile Salts ◽  
Perfused Rat Liver ◽  
Acute Effects ◽  
Calcium Fluxes ◽  
Principal Effect

The effects were investigated of the choleretic bile salt glycoursodeoxycholate (G-UDCA) and of the cholestatic bile salt taurochenodeoxycholate (T-CDCA) on changes in perfusate Ca2+, glucose and oxygen and in bile calcium and bile flow induced by the administration of (a) vasopressin, (b) glucagon and (c) glucagon plus vasopressin together to the perfused rat liver [Hamada, Karjalainen, Setchell, Millard & Bygrave (1992) Biochem. J. 281, 387-392]. G-UDCA itself increased the secretion of calcium in the bile several-fold, but its principal effect was to augment each of the above-mentioned metabolic events except glucose and oxygen output; particularly noteworthy was its ability to augment the ‘transients’ in bile calcium and bile flow seen immediately after the administration of vasopressin with or without glucagon. T-CDCA, by contrast, produced opposite effects and attenuated all of the parameters measured, and in particular the transients in bile calcium and bile flow. The data provide evidence of a strong correlation between calcium fluxes occurring on both the sinusoidal and the bile-canalicular membranes and that all are modifiable by glucagon, Ca(2+)-mobilizing hormones and bile salts.

scholarly journals Cell swelling increases bile flow and taurocholate excretion into bile in isolated perfused rat liver

1992 ◽  
Vol 281 (3) ◽  
pp. 593-595 ◽  
Author(s):  
C Hallbrucker ◽  
F Lang ◽  
W Gerok ◽  
D Häussinger
Keyword(s):  
Bile Acid ◽  
Amino Acid ◽  
Cell Volume ◽  
Rat Liver ◽  
Bile Flow ◽  
Cell Swelling ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Volume Changes ◽  
Close Relationship

The effects of aniso-osmotically and amino-acid-induced cell-volume changes on bile flow and biliary taurocholate excretion were studied in isolated perfused rat liver. With taurocholate (100 microM) in the influent perfusate, hypo-osmotic exposure (225 mosmol/l) increased taurocholate excretion into bile and bile flow by 42 and 27% respectively, whereas inhibition by 32 and 47% respectively was observed after hyperosmotic (385 mosmol/l) exposure. The effects of aniso-moticity on taurocholate excretion into bile was observed throughout aniso-osmotic exposure, even after completion of volume-regulatory ion fluxes and were fully reversible upon re-exposure to normo-osmotic media. Hypo-osmotic cell swelling (225 mosmol/l) increased the Vmax. of taurocholate translocation from the sinusoidal compartment into bile about 2-fold. Also, cell swelling induced by glutamine and glycine stimulated both bile flow and biliary taurocholate excretion. There was a close relationship between the aniso-osmotically and amino-acid-induced change of cell volume and taurocholate excretion into bile. The data suggest that liver cell volume plays an important role in regulating bile-acid-dependent bile flow and biliary taurocholate excretion.

scholarly journals Hepatic thiol and glutathione efflux under the influence of vasopressin, phenylephrine and adrenaline

1985 ◽  
Vol 226 (2) ◽  
pp. 545-549 ◽  
Author(s):  
H Sies ◽  
P Graf
Keyword(s):  
Plasma Membrane ◽  
Cyclic Amp ◽  
Rat Liver ◽  
Isolated Perfused Rat Liver ◽  
Peripheral Inflammation ◽  
Perfused Rat Liver ◽  
Dibutyryl Cyclic Amp ◽  
Hormone Dependence ◽  
Experimental Shock ◽  
Hormone Effects

Thiol and glutathione (GSH) efflux across the sinusoidal plasma membrane in isolated perfused rat liver was stimulated by addition of hormones such as vasopressin, phenylephrine and adrenaline, whereas glucagon or dibutyryl cyclic AMP were without effect. Phenylephrine and adrenaline effects were sensitive to prazosin and phentolamine, respectively. The increase in thiol efflux was largely accounted for by an increase in GSH efflux. Thiol efflux and the hormone effects were abolished in GSH-depleted liver. Biliary GSH efflux was diminished upon hormone addition. The newly discovered hormone-dependence of GSH release across the sinusoidal plasma membrane may explain the known loss of GSH during conditions of experimental shock (traumatic or endotoxin) and stress and peripheral inflammation.

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