Reversal of ammonia coma in rats by L-dopa: a peripheral effect.

Abstract

SUMMARY Ammonia coma was produced in rats within 10 to 15 minutes of an intraperitoneal injection of 1.7 mmol NH4C1. This coma was prevented with 1-68 numol L-dopa given by gastric intubation 15 minutes before the ammonium salt injection. The effect of L-dopa was correlated with a decrease in blood and brain ammonia, an increase in brain dopamine, and an increase in renal excretion of ammonia and urea. Intraventricular infusion of dopamine sufficient to raise the brain dopamine to the same extent did not prevent the ammonia coma nor affect the blood and brain ammonia concentrations. Bilateral nephrectomy eliminated the beneficial effect of L-dopa on blood and brain ammonia and the ammonia coma was not prevented. Thus, the reduction in blood and brain ammonia, and the prevention of ammonia coma after L-dopa, can be accounted for by the peripheral effect of dopamine on renal function rather than its central action. These results provide a reasonable explanation for the beneficial effects observed in some encephalopathic patients receiving L-dopa.The arousal effect of L-dopa in hepatic coma has been observed repeatedly since the original observations (Parkes et al., 1970). The arousal response is observed in approximately one-half ofpatients treated and is temporary in all but a few (Fischer et al., 1976). The beneficial effect of L-dopa has generally been presumed to be a central effect of its derivative, dopamine, and has been cited as evidence supporting the false neurotransmitter hypothesis of the aetiology of hepatic coma (Fischer and Baldessarini, 1971). We studied the effect of L-dopa in experimental ammonia coma in rats, thinking that there might be an association between the arousal effect of L-dopa and the brain ammonia concentration. We found, indeed, that L-dopa in sufficient dosage prevented ammonia coma, and that the presence or absence of coma was related to the brain ammonia but not the brain dopamine concentration. We also observed that the reduction in brain and blood ammonia after L-dopa was associated with an increase in renal excretion of ammonia and urea, and that nephrectomy eliminated the effects of L-dopa on coma and on the blood and brain ammonia concentrations.

The mechanism of hepatic coma†

“…However, experimental evidence indicates that the effect of L-dopa results from enhanced renal excretion of ammonia and urea (20). In normal rats, p.0.…”

Postischemic liver damage in rats: Amino acid analysis and morphometric studies.

“…The ammonia coma was caused in rats after an injection of NH4 Cl (Zieve et al 1979), where an increase in ammonia more than ten times that in control animals was reported. The rise in ammonia level in this series may not have any major role in the animal death.…”

Effects of Octanoic Acidemia on Palmitic Acid Metabolism in Rat Liver

“…Plasma free fatty acids were determined as described by Zieve et al (2) which recovered 80-85% of octanoic acid when added to plasma. Degree of f a t t y acidemia.…”