Inhibition of gluconeogenesis and urea synthesis in isolated rat hepatocytes by acetazolamide

1985 ◽  
Vol 13 (1) ◽  
pp. 255-255 ◽  
Author(s):  
HILARY K. METCALFE ◽  
JOHN P. MONSON ◽  
PETER J. DREW ◽  
RICHARD A. ILES ◽  
NICHOLAS D. CARTER ◽  
...  
Keyword(s):  
Rat Hepatocytes ◽  
Urea Synthesis ◽  
Isolated Rat Hepatocytes ◽  
Isolated Rat

The effect of Arginine Vasopressin on Ureagenesis in Isolated rat Hepatocytes

1985 ◽  
Vol 69 (2) ◽  
pp. 231-233 ◽  
Author(s):  
P. J. T. Drew ◽  
J. P. Monson ◽  
H. K. Metcalfe ◽  
S. J. W. Evans ◽  
R. A. Iles ◽  
...  
Keyword(s):  
Ammonium Chloride ◽  
Dose Response ◽  
Arginine Vasopressin ◽  
Response Curve ◽  
Rat Hepatocytes ◽  
Dose Response Curve ◽  
Physiological Significance ◽  
Urea Synthesis ◽  
Isolated Rat Hepatocytes ◽  
Isolated Rat

1. The effect of arginine vasopressin (AVP) on ureagenesis was measured in isolated rat hepatocytes with ammonium chloride and l(+)-lactate as substrates. 2. AVP was found to stimulate urea synthesis and the dose-response curve suggests that such an effect is present at concentrations of the hormone as low as 25-50 pmol/l. 3. Both the dose-response curve and the concentrations of NH4+ employed suggest that the effect observed could be of physiological significance.

scholarly journals NADP-specific isocitrate dehydrogenase in regulation of urea synthesis in rat hepatocytes

1980 ◽  
Vol 190 (3) ◽  
pp. 581-592 ◽  
Author(s):  
L G Petcu ◽  
G W E Plaut
Keyword(s):  
Isocitrate Dehydrogenase ◽  
Reductive Amination ◽  
Rat Hepatocytes ◽  
Urea Synthesis ◽  
Isolated Rat Hepatocytes ◽  
Lactate And Pyruvate ◽  
Rate Limiting ◽  
Isolated Rat ◽  
Reducing Equivalents

The effect of inhibition of NADP-specific isocitrate dehydrogenase (EC 1.1.1.42) by DL-threo-alpha-methylisocitrate (3-hydroxy-1,2,3-butanetricarboxylase) on urea synthesis was studied in isolated rat hepatocytes. alpha-Methylisocitrate substantially inhibited the rate of urea synthesis (35—84%) with substrates requiring net reductive amination of 2-oxoglutarate to glutamate for aspartate synthesis (i.e., L-serine, D-alanine, or NH4Cl + L-lactate). alpha-Methylisocitrate did not inhibit synthesis of urea from substrates not requiring reductive formation of glutamate (i.e. L-alanine, L-glutamine, L-asparagine, or NH4Cl + L-ornithine). The rate-limiting role of NADPH in urea synthesis was correlated with the decrease in NADPH content that occurred upon addition of NH4Cl or of alpha-methylisocitrate to hepatocytes incubated with lactate and pyruvate, indicating utilization of NADPH for reductive amination of 2-oxoglutarate and inhibition of NADPH generation via NADP-isocitrate dehydrogenase, respectively. Similar results were obtained with D-alanine and L-serine; however, alpha-methylisocitrate or NH4Cl did not substantially decrease NADPH content when L-alanine was the substrate. Inhibitors or ornithine—2-oxo acid transaminase (L-canaline or gabaculine) decreased the uptake of ornithine by hepatocytes and inhibited the alpha-methylisocitrate insensitive urea synthesis from ornithine and NH4Cl. Canaline did not inhibit urea synthesis from lactate, ornithine, and NH4Cl but the inhibition by alpha-methylisocitrate of urea formation from this combination was appreciably larger with canaline (approx. 82%) than without canaline (approx. 48%). Inhibition of urea synthesis from NH4Cl + lactate by alpha-methylisocitrate was partially prevented by oleate, octanoate, or 3-hydroxybutyrate. When the NADH content of hepatocytes was increased by 3-hydroxybutyrate, the addition of NH4Cl and/or alpha-methylisocitrate caused a decline in NADH (and NADPH) content, suggesting that reducing equivalents from NADH as well as from NADPH can support net reductive amination of 2-oxoglutarate when required for urea synthesis.

The Effect of Oxygen Transport Resistances on the Viability and Functions of Isolated Rat Hepatocytes

1996 ◽  
Vol 19 (1) ◽  
pp. 61-71 ◽  
Author(s):  
G. Catapano ◽  
L. De Bartolo ◽  
C.P. Lombardi ◽  
E. Drioli
Keyword(s):  
Oxygen Transport ◽  
Elimination Rate ◽  
Rat Hepatocytes ◽  
Isolated Hepatocytes ◽  
Urea Synthesis ◽  
Liver Support ◽  
Isolated Rat Hepatocytes ◽  
Cell Culture Techniques ◽  
Bioartificial Liver Support ◽  
Isolated Rat

The treatment of fulminant hepatic failure with a bioartificial liver support device relies on the possibility of replacing the detoxification and synthetic functions of the injured liver for as long as needed for patient recovery. In spite of progress in cell culture techniques, the effective use of isolated hepatocytes in liver support devices is currently hampered by a lack of information on the metabolic factors limiting long term hepatocyte culture. In this paper, we report our investigation on the effects of oxygen transport resistances on the viability and functions of isolated rat hepatocytes cultured on collagen coated Petri dishes. Detoxification and synthetic functions of the hepatocytes were studied with respect to ammonia and phenolsulphonphthalein elimination and urea synthesis. Lower resistances to oxygen transport favored hepatocyte survival. The isolated hepatocytes synthesized urea at rates that decreased as the resistance to oxygen transport increased. The rate at which urea was synthesized also decreased during the culture. Neither PSP, nor ammonia elimination rate was greatly affected by increasing oxygen transport resistances and remained rather constant up to a week of culture.

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