Dopamine: Mediator of Brain Polysome Disaggregation after L-Dopa

Weiss, B.; Munro, Hamish N.; Ordóñez, Luis A.; Wurtman, Richard J.

doi:10.1126/science.177.4049.613

Cited by 40 publications

(11 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These effects may result from the competitive displacement of the true neurotransmitter by the newly-formed DA [27--30]. L-dopa administration has also been shown to cause a marked disaggregation of brain polysomes [31,32]. The magnitude o.f this effect requires that the changes occur in all, or almost all, of the cells in the brain.…”

Section: Discussionmentioning

confidence: 99%

“…The magnitude o.f this effect requires that the changes occur in all, or almost all, of the cells in the brain. Polysome disaggregation is blocked in animals pretreated with a decarboxylase inhibitor, but is potentiated by monoamine oxidase inhibitors [32]. Disaggregation probably thus results from an action of DA within the great majority of brain cells that do not normally contain this monoamine [32].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The effects of 6-hydroxydopamine pretreatment on the accumulation of dopa and dopamine in brain and peripheral organs following l-dopa administration

Lytle

Hurko

Romero

et al. 1972

J. Neural Transmission

View full text Add to dashboard Cite

SummaryThe capacity of brain and peripheral organs to accumulate dopamine following intraperitoneal 1-dopa was not impaired in rats whose catecholamine-containing nerve terminals had been destroyed by pretreatment with intracisternal or intraperitoneal 6-hydroxydopamine. These findings indicate that the uptake of exogenous 1-dopa and its conversion to dopamine are not restricted to cells that normally synthesize and contain catecholamines.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The effects of 6-hydroxydopamine pretreatment on the accumulation of dopa and dopamine in brain and peripheral organs following l-dopa administration

Lytle

Hurko

Romero

et al. 1972

J. Neural Transmission

View full text Add to dashboard Cite

show abstract

“…While L-dopa is the amino acid precursor of both dopamine and noradrenaline, its administration to rats increases the brain levels of dopamine but, even in very high doses, the level of noradrenaline is only slightly raised (Weiss et al, 1972). The administration of L-dopa to man in fact leads to a significant decrease in the output of noradrenaline metabolites (O'Gorman et al, 1970).…”

Section: Dopamine-inhibitory Controlmentioning

confidence: 99%

The Role of Serotonin and Dopamine in Hypothalamic‐pituitary Function

Smythe¹

1977

Clinical Endocrinology

View full text Add to dashboard Cite

“…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.…”

mentioning

confidence: 99%

D-amphetamine disaggregates brain polysomes via a dopaminergic mechanism.

Moskowitz¹,

Weiss²,

Lytle³

et al. 1975

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

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...

show abstract

Dopamine: Mediator of Brain Polysome Disaggregation after L-Dopa

Cited by 40 publications

References 14 publications

The effects of 6-hydroxydopamine pretreatment on the accumulation of dopa and dopamine in brain and peripheral organs following l-dopa administration

The effects of 6-hydroxydopamine pretreatment on the accumulation of dopa and dopamine in brain and peripheral organs following l-dopa administration

The Role of Serotonin and Dopamine in Hypothalamic‐pituitary Function

D-amphetamine disaggregates brain polysomes via a dopaminergic mechanism.

Contact Info

Product

Resources

About