Cell Volume Regulatory Responses of Isolated Perfused Rat Liver. The Effect of Amino Acids

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.

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The effects of amino acids on albumin synthesis by the isolated perfused rat liver

Biochemical Journal ◽

10.1042/bj1290805 ◽

1972 ◽

Vol 129 (4) ◽

pp. 805-809 ◽

Cited By ~ 29

Author(s):

L. Kelman ◽

S. J. Saunders ◽

S. Wicht ◽

L. Frith ◽

A. Corrigall ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Rat Liver ◽

Normal Values ◽

Isolated Perfused Rat Liver ◽

Perfused Rat Liver ◽

Albumin Synthesis ◽

Isoleucine Leucine ◽

Blood Concentrations ◽

Normal Peripheral Blood

Albumin synthesis was measured in the isolated perfused rat liver by using the livers of both well-fed and starved rats. Starvation markedly decreased albumin synthesis. The livers from starved rats were unable to increase synthesis rates after the addition to the perfusates of single amino acids or the addition of both glucagon and tryptophan. Arginine, asparagine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan and valine, added together to ten times their normal peripheral blood concentrations, restored synthesis rates to normal. The plasma aminogram (i.e. the relative concentrations, of amino acids) was altered by depriving rats of protein for 48h. The use of blood from the deprived rats as perfusate, instead of normal blood, decreased albumin synthesis rates significantly by livers obtained from well-fed rats. The addition of single amino acids, including the non-metabolizable amino acid, α-aminoisobutyric acid, to the above mixture increased albumin synthesis rates to normal values. It is concluded that amino acids play an important role in the control of albumin synthesis and that more than one mechanism is probably involved.

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Hepatic synthesis of carnitine from protein-bound trimethyl-lysine. Lysosomal digestion of methyl-lysine-labelled asialo-fetuin

Biochemical Journal ◽

10.1042/bj1600085 ◽

1976 ◽

Vol 160 (1) ◽

pp. 85-95 ◽

Cited By ~ 76

Author(s):

J LaBadie ◽

W A Dunn ◽

N N Aronson

Keyword(s):

Amino Acids ◽

Rat Liver ◽

Free Amino ◽

Isolated Perfused Rat Liver ◽

Methyl Groups ◽

Second Derivative ◽

Perfused Rat Liver ◽

Lysine Residues ◽

Derivatives Of ◽

Hepatic Synthesis

The biosynthesis of carnitine in the rat was studied by following the metabolism of two radioactive derivatives of asialo-fetuin. The first contained 14C-labelled methyl groups covalently bound to the 6-N-amino fraction of its lysine residues as 6-N-monomethyl- and dimethyl-lysine. By treating this protein with iodomethane, a second derivative was produced in which the radioactivity was preferentially incorporated as 6-N-[Me-14C]-trimethyl-lysine. These desialylated glycoproteins, like other asialo-proteins, were immediately cleared from the blood by rat liver. Within hepatocyte lysosomes, the 14C-labelled proteins were rapidly hydrolysed, producing free amino acids containing the various 6-N-[Me-14C]methylated lysine residues. The radioactive amino acids crossed the lysosomal membrane and were further metabolized in the cytosol. Carnitine was the major radioactive metabolite detected in extracts of the rat carcass and liver after intravenous injection of 6-N-[Me-14C]trimethyl-lysine-labelled asialo-fetuin. Within 3h, at least 34.6% of the trimethyl-lysine in the administered protein was converted into carnitine. Similarly, an isolated perfused rat liver converted 30% of the added peptide-bound trimethyl-lysine into carnitine within 90 min. On the other hand, in numerous attempts we failed to detect radioactive carnitine in both rat liver and carcass between 20 min and 22 h after injection of 6-N-[Me-14C]-monomethyl- and -dimethyl-lysine-labelled asialo-fetuin. These data provide evidence for a pathway of carnitine biosynthesis that involves trimethyl-lysine as a peptide-bound precursor as proposed by R.A. Cox & C.L. Hoppel [(1973) Biochem. J. 136, 1083-1090] and V. Tanphaichitr & H.P. Broquist [(1973) J. Biol. Chem. 248, 2176-2181]. The findings also show that rat liver can synthesize carnitine without the aid of other tissues, but cannot convert free partially methylated lysines into trimethyl-lysine.

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Cell-swelling-induced taurine release from isolated perfused rat liver

Biochemistry and Cell Biology ◽

10.1139/o94-002 ◽

1994 ◽

Vol 72 (1-2) ◽

pp. 8-11 ◽

Cited By ~ 4

Author(s):

H. S. Brand ◽

A. J. Meijer ◽

L. A. Gustafson ◽

G. G. A. Jörning ◽

A. C. J. Leegwater ◽

...

Keyword(s):

Amino Acids ◽

Rat Liver ◽

Cell Swelling ◽

Isolated Perfused Rat Liver ◽

Perfused Rat Liver ◽

Liver Mass ◽

Taurine Release ◽

Perfusion Medium ◽

Nacl Concentration ◽

Isolated Liver

Astrocytes and lymphocytes are able to release significant amounts of taurine during periods of hypotonicity to reduce the increase in cell volume. To investigate this mechanism in the liver, we studied the release of free amino acids from isolated perfused rat liver during hypotonicity. The osmolarity of the perfusion medium was reduced from 305 to 255 or 205 mosM by decreasing the NaCl concentration 25 or 50 mM, respectively. This induced an 6–8% increase in liver mass and was associated with a specific 1.7-fold (−50 mosM) and 14-fold (−100 mosM) increase of the taurine release. None of the other amino acids measured showed a significant increase in their concentration in the effluent. The increase in taurine release occurred within 30 s after exposure to hypotonicity (maximal after 1–1.5 min) and followed closely the changes in liver mass. The taurine release declined gradually during successive exposures of the isolated liver to −100 mosM. This release was 29 and 17% of the original during the second and third exposure, respectively.Key words: cell swelling, liver, taurine.

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