One hour after administration of L-dopa (50 to 300 milligrams per kilogram), there is a marked disaggregation of brain polysomes in immature rats. Adult animals show a similar response, but require larger doses of the amino acid (500 milligrams per kilogram). Single doses of L-dopa significantly elevate amounts of tryptophan in the brain; hence their effect on polysomes does not result from the unavailability of this amino acid.

The disaggregation of brain polysomes which is produced by giving large doses of (L)-dopa to rats is not reproduced by administering its metabolite, 3-O-methyldopa, by giving D-dopa, which also depletes the brain of S-adenosylmethionine but is not converted to catecholamines, or by giving the L-dopa after a decarboxylase inhibitor. Polysome disaggregation is potentiated by the prior administration of a monoamine oxidase inhibitor, indicating that formation of a catecholamine is an obligatory requirement. These observations suggest that the mechanism by which L-dopa disaggregates brain polysomes involves its conversion to dopamine within the majority of brain cells.

Brain polysomes are disaggregated in rats given moderate to large doses of d-amphetamine sulfate; this response is rapid in onset, lasts for at least 4-6 hr, and varies with the age of the animal. Pretreatment with a dopamine receptor blocking agent, haloperidol or pimozide, blocks the amphetamine-induced disaggregation.Rats treated with large single doses of i-dopa (a catecholamine precursor) exhibit a major disaggregation of brain polysomes (1) and a parallel decrease in the net rate of brain protein synthesis (2, 3). The L-dopa-induced disaggregation of brain polysomes is suppressed in animals pretreated with drugs that block the conversion of dopa to dopamine, or with drugs that block dopamine receptors (4, 5). Hence, the drug-induced polysome disaggregation may result from a direct action of dopamine on a receptor that controls the intracellular proteinsynthetic apparatus.Amphetamine, a sympathomimetic agent, acts on the central nervous system to affect locomotor activity (6-9), appetite (10), and thermoregulation (11-14); in high doses, it causes a psychotic reaction in humans that resembles paranoid schizophrenia (15). Catecholamine-containing brain neurons appear to mediate many of the behavioral and physiological effects of this drug (16). Relatively little information exists regarding effects of amphetamine on brain protein synthesis. We now report that large doses of d-amphetamine sulfate disaggregate brain polysomes in rats, and that this effect, like that of -dopa, appears to be mediated by dopamine receptors. MATERIALS AND METHODSMale albino rats of various ages (Charles River Laboratories, Wilmington, Mass.) were exposed to light from 9 a.m. to 9 p.m. and given free access to food and water. All animals were maintained at ambient temperatures ranging from 20-22'. Animals less than 26 days of age remained with the dam in litters of eight pups; older animals were caged in groups of four for 1 day prior to an experiment. All injections were administered intraperitoneally.Polysomes were prepared as described (1, 4). Briefly, the brains were removed, pooled two per sample, minced, and homogenized in an ice-cold 0.25 M sucrose medium containing 0.05 M Tris, HCl, 0.10 M KCl, and 0.012 M MgCl2, at pH 7.6. The homogenates were then centrifuged for 20 min at 21,000 X g; the post-mitochondrial supernatants were treated with sodium deoxycholate to a concentration of 1% and then layered over discontinuous sucrose gradients (0.5 M, 2.0 M). After this centrifugation, the pellets of ribosomes were again suspended and applied to a 10-40% continuous sucrose gradient. Absorbance profiles were recorded at 260 nm. The percentage of polysomes in the profile represents the fraction of total area attributable to polyribosomes (1, 4, 5). RESULTSIn the first experiment, 26-day-old animals received 0.9% (w/v) saline vehicle (1 ml/kg) or d-amphetamine sulfate (1.5, 10, 15, or 50 mg/kg, salt weight); they were decapitated 1 hr later. Doses of 10 mg/kg of d-amphetamine or larger disaggregated the brain polysomes; the m...

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Summary. Ethanol inhibits the oxidation of ethylene glycol by horse liver alcohol dehydrogenase, beef liver catalase, and crude rat liver homogenates. The inhibition of alcohol dehydrogenase is of the competitive type, with a K(r) of 1.9 mM at pH 8.0, at which the K(m) for ethylene glycol is 38 mM. Theoretically, the generation of H(2)0(2), a by-product of the oxidation of ethanol by liver homogenates, could increase the oxidation of ethylene glycol via catalase, but this tendency is outweighed by the inhibitory effect of ethanol on this reaction. The results provide a theoretical basis for the use of ethanol in ethylene glycol intoxication in humans.