Reversal ofammonia coma inratsbyL-dopa: aperipheral effect
摘要
SUMMARY Ammoniacoma was produced inratswithin 10to15minutes ofan intraperitoneal injection of1.7mmolNH4C1. This coma was prevented with1-68 numolL-dopa given bygastric intubation 15minutes before theammoniumsalt injection. Theeffect ofL-dopa was correlated with a decrease inbloodandbrain ammonia, an increase inbraindopamine, andan increase in renal excretion ofammoniaandurea.Intraventricular infusion ofdopamine sufficient toraise the brain dopamine tothesame extent didnotprevent theammonia coma nor affect thebloodand brain ammoniaconcentrations. Bilateral nephrectomy eliminated thebeneficial effect ofL-dopa on bloodandbrain ammoniaandtheammonia coma was notprevented. Thus, thereduction in blood andbrain ammonia, andtheprevention ofammonia coma after L-dopa, can beaccounted forbytheperipheral effect ofdopamine on renal function rather thanitscentral action. These results provide areasonable explanation forthebeneficial effects observed insome encephalopathic patients receiving L-dopa. Thearousal effect ofL-dopa inhepatic comahas beenobserved repeatedly since theoriginal observations (Parkes etal., 1970). Thearousal response is observed inapproximately one-half ofpatients treated andistemporary inallbutafew(Fischer etal., 1976). Thebeneficial effect ofL-dopa hasgenerally beenpresumed tobeacentral effect ofits derivative, dopamine, andhasbeencited asevidence supporting thefalse neurotransmitter hypothesis oftheaetiology ofhepatic coma(Fischer andBaldessarini, 1971). Westudied theeffect ofL-dopa inexperimental ammonia comainrats, thinking that there might be anassociation between thearousal effect ofL-dopa andthebrain ammoniaconcentration. We found, indeed, thatL-dopa insufficient dosage prevented ammoniacoma,andthatthepresence orabsence ofcomawasrelated tothebrain ammoniabutnot thebrain dopamine concentration. Wealso observed thatthereduction inbrain andbloodammonia after L-dopa wasassociated with anincrease inrenal excretion ofammonia andurea, andthat nephrectomyelimi