Role of the hepatic function in the development of the pyrogenic tolerance to muramyl dipeptide

We have demonstrated that the hepatic function may have an important role in the development of tolerance to the pyrogenic effect induced by endotoxin. To further investigate if the role of the hepatic function in the development of tolerance also extends to that induced by other pyrogenic stimuli, we investigated the effect of galactosamine, a specific inhibitor of the hepatic protein synthesis, on the development of tolerance to the pyrogenic effect induced by muramyl dipeptide (MDP) in rats. Pyrogenic tolerance was observed after the second intravenous or intraperitoneal injection of MDP (500 μg/kg), 24 h after the first injection, similar to what was observed with endotoxin. Pyrogenic tolerance was abolished when galactosamine (300 mg/kg ip) was injected simultaneously with MDP (500 μg/kg iv) on the first day. When uridine (600 mg/kg ip) was administered simultaneously with galactosamine (300 mg/kg ip) and the first injection of MDP (500 μg/kg ip), pyrogenic tolerance was again observed after the second injection of the peptidoglycan. In conclusion, the hepatic function may not be important only for the development of tolerance to endotoxin, but also to a totally different pyrogenic stimulus such as MDP.

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Key role of l-alanine in the control of hepatic protein synthesis

Biochemical Journal ◽

10.1042/bj2410491 ◽

1987 ◽

Vol 241 (2) ◽

pp. 491-498 ◽

Cited By ~ 26

Author(s):

D Pérez-Sala ◽

R Parrilla ◽

M S Ayuso

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Physiological Role ◽

Chain Elongation ◽

Liver Protein ◽

Isolated Liver Cells ◽

Metabolic Transformation ◽

Hepatic Protein Synthesis

We investigated the effects of administration of single amino acids to starved rats on the regulation of protein synthesis in the liver. Of all the amino acids tested, only alanine, ornithine and proline promoted statistically significant increases in the extent of hepatic polyribosome aggregation. The most effective of these was alanine, whose effect of promoting polyribosomal aggregation was accompanied by a decrease in the polypeptide-chain elongation time. The following observations indicate that alanine plays an important physiological role in the regulation of hepatic protein synthesis. Alanine was the amino acid showing the largest decrease in hepatic content in the transition from high (fed) to low (starved) rates of protein synthesis. The administration of glucose or pyruvate is also effective in increasing liver protein synthesis in starved rats, and their effects were accompanied by an increased hepatic alanine content. An increase in hepatic ornithine content does not lead to an increased protein synthesis, unless it is accompanied by an increase of alanine. The effect of alanine is observed either in vivo, in rats pretreated with cycloserine to prevent its transamination, or in isolated liver cells under conditions in which its metabolic transformation is fully impeded.

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ROLE OF THE STATE OF REDUCTION OF THE NAD SYSTEM AND cAMP ON THE MECHANISM OF THE GLUCAGON INDUCED INHIBITION OF HEPATIC PROTEIN SYNTHESIS

Biochemical Society Transactions ◽

10.1042/bst009305p ◽

1981 ◽

Vol 9 (2) ◽

pp. 305P-305P

Author(s):

M. S. Ayuso ◽

P. Vega ◽

R. Parrilla

Keyword(s):

Protein Synthesis ◽

The State ◽

Role Of The State ◽

Hepatic Protein Synthesis

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Differential feeding responses to bacterial lipopolysaccharide and muramyl dipeptide

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1991.261.3.r659 ◽

1991 ◽

Vol 261 (3) ◽

pp. R659-R664 ◽

Cited By ~ 11

Author(s):

W. Langhans ◽

G. Balkowski ◽

D. Savoldelli

Keyword(s):

Food Intake ◽

Intraperitoneal Injection ◽

Bacterial Infections ◽

Muramyl Dipeptide ◽

Bacterial Lipopolysaccharide

The present study was designed to test whether a tolerance to the hypophagic effects of bacterial lipopolysaccharide (LPS) and muramyl dipeptide (MDP) develops with repeated injections in rats and whether a relationship between the hypophagic effects of both compounds exists. Only the first of three subsequent intraperitoneal injection of LPS (100 micrograms/kg body wt each), given every 2nd day, led to a significant reduction of food intake. In contrast, MDP (1.6 mg/kg body wt) did not lose its hypophagic effect with four subsequent intraperitoneal injections. Furthermore, the LPS tolerance did not alter the hypophagic response to subsequently injected MDP. Likewise, MDP pretreatment did not alter the hypophagic response to LPS. Doses of MDP and LPS that were individually below the threshold for a reliable reduction of food intake (0.4 mg MDP/kg body wt + 25 micrograms LPS/kg body wt) reduced food intake synergistically when injected together. The hypophagia produced by combined injections of MDP plus LPS slowly diminished with repeated injections. The results indicate that separate but interacting mechanisms are involved in the feeding responses to MDP and LPS. The observed synergism between MDP and LPS suggests a synergistic role of bacterial muramyl peptides and LPS in the anorexia during bacterial infections.

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Role of the state of reduction of the nad system on the regulation of hepatic protein synthesis in the rat in vivo

International Journal of Biochemistry ◽

10.1016/0020-711x(82)90045-3 ◽

1982 ◽

Vol 14 (7) ◽

pp. 615-620 ◽

Cited By ~ 7

Author(s):

Sebastian Cerdan Garcia-Esteller ◽

SofÍa Sanchez Robles ◽

Angeles Martin-Requero ◽

Matilde S. Ayuso-Parrilla ◽

Roberto Parrilla

Keyword(s):

Protein Synthesis ◽

The State ◽

Role Of The State ◽

Hepatic Protein Synthesis

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Effect of heat stress on LPS-induced febrile response ind-galactosamine-sensitized rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2001.280.2.r338 ◽

2001 ◽

Vol 280 (2) ◽

pp. R338-R344 ◽

Cited By ~ 12

Author(s):

Karol Dokladny ◽

Anna Kozak ◽

Maciej Wachulec ◽

Erik S. Wallen ◽

Margaret G. Menache ◽

...

Keyword(s):

Protein Synthesis ◽

Heat Stress ◽

Heat Exposure ◽

Hepatic Function ◽

Liver Protein ◽

Hsp 70 ◽

Febrile Response ◽

Tnf Α ◽

Necrosis Factor

We have previously reported that heat conditioning augments lipopolysaccharide (LPS)-induced fever in rats, which is accompanied by an accumulation of heat shock protein (HSP) in the liver and the reduction of the plasma level of tumor necrosis factor (TNF-α) (Kluger MJ, Rudolph K, Soszynski D, Conn CA, Leon LR, Kozak W, Wallen ES, and Moseley PL. Am J Physiol Regulatory Integrative Comp Physiol 273: R858–R863, 1997). In the present study we have tested whether inhibition of protein synthesis in the liver can reduce the effect of this heat conditioning on the LPS-induced febrile response in the rat.d-galactosamine (d-gal) was used to selectively inhibit liver protein synthesis. d-gal (500 mg/kg) or PBS as control was administered intraperitoneally 1 h before heat stress. LPS (50 μg/kg ip) was injected 24 h post-heat exposure. Treatment with d-gal blunted the febrile response to LPS. Moreover, heat-conditioned rats treated first with d-gal and subsequently with LPS demonstrated a profound fall in core temperature 10–18 h post-LPS. A significant increase of serum TNF-α accompanied this effect of d-gal on fever. Heat-conditioned animals receiving d-gal showed an inhibition in inducible HSP-70 in the liver. These data support the role of hepatic function in modulating the febrile response to LPS.

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