L-Dopa: Disaggregation of Brain Polysomes and Elevation of Brain Tryptophan

Weiss, B.; Munro, Hamish N.; Wurtman, Richard J.

doi:10.1126/science.173.3999.833

Cited by 63 publications

(20 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effect on the UFA-tryptophan system of L-DOPA is consistent with the increases in the concentrations of brain tryptophan (Weiss, Munro & Wurtman, 1971) and plasma UFA (RiveraCalimlim & Bianchine, 1972) reported to occur after injection of this drug in high dosage.…”

Section: Discussionsupporting

confidence: 85%

Effects on Plasma and Brain Tryptophan in the Rat of Drugs and Hormones That Influence the Concentration of Unesterified Fatty Acid in the Plasma

Curzon¹,

Knott²

1974

British J Pharmacology

143

View full text Add to dashboard Cite

1 The effects on tryptophan distribution and metabolism of drugs altering plasma unesterified fatty acid (UFA) concentration were investigated in the rat. 2 UFA and plasma free (i.e. ultrafilterable) tryptophan altered in the same direction. 3 Catecholamines and L-DOPA increased both plasma UFA and free tryptophan. L-DOPA also increased brain tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) but decreased brain 5-hydroxytryptamine (5-HT). 4 Aminophylline increased plasma UFA and free tryptophan and also brain tryptophan, 5-HT and 5-HIAA. Food deprivation had qualitatively similar effects. 5 Insulin decreased plasma UFA and free tryptophan in both fed and food-deprived rats. However, while in fed rats these changes were associated with small decreases of brain indoles, in food-deprived animals small increases occurred. 6 Nicotinic acid had only small effects in fed rats but it opposed both the UFA and indole changes in food-deprived animals. Total plasma tryptophan increased in nicotinic acid treated, food-deprived rats. 7 There was a tendency towards inverse relations between changes of plasma free and total tryptophan. 8 The results suggest that drugs which influence plasma UFA through actions on cyclic AMP thereby alter the binding of tryptophan to plasma protein and that this leads to altered distribution and metabolism of tryptophan.

show abstract

Section: Discussionsupporting

confidence: 85%

Effects on Plasma and Brain Tryptophan in the Rat of Drugs and Hormones That Influence the Concentration of Unesterified Fatty Acid in the Plasma

Curzon¹,

Knott²

1974

British J Pharmacology

143

View full text Add to dashboard Cite

show abstract

“…Possible relationship to ATP level, pH and other factors has been discussed for progressive cerebral ischemia and anoxia. 11 mon during the early stage of cerebral ischemia, and intermittent seizure activity does not affect polypeptide synthesis in this experimental model. 3 -' Since our previous investigation did not show much effect of pH 5 factor from ischemic tissue, 21 pH 5 factor was prepared only from normal tissue.…”

Section: Discussionmentioning

confidence: 62%

“…The procedure for preparation of polyribosomes is based on the method of Weiss et al 11 as described previously 12 with some modification. Cerebral hemispheres were homogenized with 0.25M sucrose (ribonuclease-free) in TKMM buffer (Tris-HCl, 50 mM at pH 7.4; KC1, 25 mM; MgCl a , 10 mM and 2-mercaptoethanol, 5 mM) by 10 up-and-down strokes in a motor-driven Teflon-glass homogenizer, and centrifuged at 12,000 g for 20 min.…”

Section: Preparation Of Polyribosomes Microsomes and Ph 5 Factormentioning

confidence: 99%

Cerebral ischemia in gerbils: polyribosomal function during progression and recovery.

Morimoto¹,

Yanagihara²

1981

Stroke

View full text Add to dashboard Cite

ReferencesWexler BC: Effect of an oral contraceptive drug on nonarteriosclerotic male and female virgin rats vs arteriosclerotic, male and female breeder rats. Angiology 25: 197-227, 1974 Aoki K: Experimental studies on the relationship between endocrine organs and hypertension in spontaneously hypertensive rats. I. Effects of hypophyscctomy, adrenalectomy, thyroidectomy, nephrectomy and sympathectomy on blood pressure. Jpn Heart J 4: 443^61, 1963

show abstract

“…These age-dependent changes may reflect ontogenetic changes in synaptogenesis or in the proteinsynthetic mechanisms within individual brain cells. The relative insensitivity of infant rats to amphetamine treatment contrasts with their heightened sensitivity to dopa-induced disaggregation (1 (27). The time course of the amphetamine-induced polysome disaggregation coincides with those of numerous other behavioral and physiological effects of amphetamine.…”

Section: Discussionmentioning

confidence: 88%

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

L-Dopa: Disaggregation of Brain Polysomes and Elevation of Brain Tryptophan

Cited by 63 publications

References 17 publications

Effects on Plasma and Brain Tryptophan in the Rat of Drugs and Hormones That Influence the Concentration of Unesterified Fatty Acid in the Plasma

Effects on Plasma and Brain Tryptophan in the Rat of Drugs and Hormones That Influence the Concentration of Unesterified Fatty Acid in the Plasma

Cerebral ischemia in gerbils: polyribosomal function during progression and recovery.

D-amphetamine disaggregates brain polysomes via a dopaminergic mechanism.

Contact Info

Product

Resources

About