Metabolism of monoamines in the brain after total hepatectomy in the rat

Bugge, Mogens; Bengtsson, Finn; Nobin, Anders; Jeppsson, Bengt; Herlin, P.

doi:10.1016/0014-4886(86)90267-0

Cited by 18 publications

(14 citation statements)

References 21 publications

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“…The marked increase in 5-HJAA concentrations and the slight increase in serotonin levels in rats with HE in this study are in agreement with the findings in other experimental models of HE ( Augmented serotonin synthesis and/or serotonin turnover have been observed in portacaval shunted rats (22) and in rats after total hepatectomy (10,14). The results of this study support a role of the changed molar ratio of BCAA and AAA mediating the augmented synthesis of serotonin and 5-HIAA (3).…”

Section: Systemssupporting

confidence: 93%

Increased serotoninergic and noradrenergic activity in hepatic encephalopathy in rats with thioacetamide—induced acute liver failure

et al. 1990

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Functional changes of various neurotransmitter systems have been implicated in the pathogenesis of hepatic encephalopathy. In this study the role of brain monoaminergic neurotransmitter systems in hepatic encephalopathy was investigated in rats with thioacetamide-induced acute liver failure. Concentrations of serotonin, dopamine, noradrenaline and of their metabolites 5-hydroxyindoleacetic acid, dihydroxyphenylalanine (following inhibition of dihydroxyphenylalanine-decarboxylase), dihydroxyphenylacetic acid, homovanillic acid and 3-methoxy-4-hydroxyphenyl-glycol, were measured in the cerebral cortex, striatum and hippocampus by high performance liquid chromatography with electrochemical detection. In hepatic encephalopathy concentrations of 5-hydroxyindoleacetic acid were increased in all three brain areas (196%, 204% and 264% of saline-treated controls, p less than 0.01), and concentrations of serotonin were increased in the frontal cortex (121%, p less than 0.01). In the frontal cortex and hippocampus of encephalopathic rats dopamine levels were increased (157% and 289%, p less than 0.05), and levels of noradrenaline (53% and 46%, p less than 0.05) were decreased associated with increased 3-methoxy-4-hydroxyphenylglycol levels (173% and 206%, p less than 0.05). The extent of these changes correlated with the stage of hepatic encephalopathy. In hepatic encephalopathy dihydroxyphenylalanine accumulation was increased in the hippocampus and unchanged in the cerebral cortex. Dopamine, noradrenaline, dihydroxyphenylacetic acid and homovanillic acid concentrations were unchanged in the striatum. The results of this study indicate that hepatic encephalopathy in thioacetamide-induced acute liver failure in rats is associated with neurochemical changes, suggesting an increased activity of the noradrenergic and serotoninergic neurotransmitter systems.

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Section: Systemssupporting

confidence: 93%

Increased serotoninergic and noradrenergic activity in hepatic encephalopathy in rats with thioacetamide—induced acute liver failure

et al. 1990

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“…In addition, in animals exposed to total liver ischaemia (Expt. II) plasma Table 1 [1,2,4,22]. In addition, in Expt.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, in Expt. II the concentrations of DOPA, DA and NE were analysed with a radio-enzymatic method in all regions [4,26].…”

Section: Methodsmentioning

confidence: 99%

The effect of liver ischaemia on brain monoamine synthesis in the rat

et al. 1987

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Subtotal or total liver ischaemia was induced in the rat by dividing the hepatic artery (Expt. I) or by total dearterialisation of the liver (Expt. II) 2 days after porta-caval shunt (PCS). The animals received i.v. a 10% glucose infusion for 5 h after the last operation and were killed by decapitation. At the end of the experiment all animals with liver ischaemia were in Grade III coma. In different regions of the CNS 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), were analysed by HPLC-technique with electrochemical detection, while dihydroxyphenylalanine (DOPA), dopamine (DA) and norepinephrine (NE) were analysed with a radio enzymatic method after blocking the decarboxylation of 5-HTP to 5-HT and DOPA to DA by inhibition of the aromatic amino acid decarboxylase enzyme with m-hydroxybenzylhydrazine (NSD 1015) in order to estimate the synthesis rate of 5-hydroxyindoles and catecholamines. In Expt. I concentrations of 5-HTP in animals with PCS were increased as compared to sham operation. In animals with liver ischaemia, 5-HTP concentrations were increased as compared to sham operation but similar to those in animals with PCS alone. These results suggest that ligation of the hepatic artery for 5 h in PCS animals does not further accelerate the rate of brain indole synthesis. In Expt. II, the 5-HTP concentrations were increased in PCS animals as compared to sham operation. Animals with total liver dearterialisation exhibited decreased 5-HTP levels as compared to PCS, suggesting a decreased brain indole synthesis after severe liver ischaemia. In Expt. II, CNS concentrations of DOPA following PCS were unaltered as compared with sham-operated animals. In animals with total liver dearterialisation, DOPA levels were increased, suggesting an augmented catecholamine synthesis. The NE levels were lower than in PCS and in sham-operated animals.

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“…In each brain region analysis of 5-HTP, serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) was performed by high pressure liquid chromatography (HPLC) with electrochemical detection [1,6]. The concentrations of DOPA, DA, and NE in the cortex, striatum, and mesencephalon-pons were determined by a radioenzymatic method [6,30].…”

Section: Methodsmentioning

confidence: 99%

“…The concentrations of DOPA, DA, and NE in the cortex, striatum, and mesencephalon-pons were determined by a radioenzymatic method [6,30].…”

Section: Methodsmentioning

confidence: 99%

The effect of ammonia infusion on brain monoamine metabolism in portacaval-shunted rats

et al. 1989

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The effect of ammonia infusion on monoamine metabolism was studied in the rat brain. Seven days after portocaval shunt (PCS) or sham operation animals were infused with ammonia or saline. Brain metabolism of serotonin and norepinephrine was studied after injection of a decarboxylase inhibitor (m-hydroxybenzylhydrazine, NSD 1015) which blocks the conversion of 5-hydroxytryptophan to serotonin and dihydroxyphenylalanine to dopamine. Neurologic testing was conducted before killing. Plasma and brain amino acids were measured. PCS animals infused with ammonia were in deep coma after 6 h infusion, whereas sham-operated animals were virtually unaffected. Brain amino acid analyses demonstrated increased concentrations of the aromatic amino acids and a tenfold increase in glutamine. Serotonin metabolism was diminished after 6 h. Dopamine synthesis was normal, but norepinephrine levels were low after 6h. The study suggests that hyperammonemia in PCS rats results in a depression of the serotonin synthesis rate in accordance with two previous studies but in contrast to previous hypotheses on the regulation of serotonin metabolism.

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Metabolism of monoamines in the brain after total hepatectomy in the rat

Cited by 18 publications

References 21 publications

Increased serotoninergic and noradrenergic activity in hepatic encephalopathy in rats with thioacetamide—induced acute liver failure

Increased serotoninergic and noradrenergic activity in hepatic encephalopathy in rats with thioacetamide—induced acute liver failure

The effect of liver ischaemia on brain monoamine synthesis in the rat

The effect of ammonia infusion on brain monoamine metabolism in portacaval-shunted rats

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