Journal ArticleDOI
The mechanism of perturbation in monoamine metabolism by L-DOPA therapy: in vivo and in vitro studies
Wakako Maruyama,Makoto Naoi,Akira Takahashi,H. Watanabe,Y. Konagaya,K. Mokuno,S. Hasegawa,Daiichiro Nakahara +7 more
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TLDR
It was proved that L-3-O-methyldopa was taken up into monoamine neurons by transport system specific for aromatic L-amino acids and inhibited transport of L-DOPA and other amino acids competitively.Abstract:
In the cerebrospinal fluid of the patients with Parkinson's disease treated with L-DOPA, L-3-O-methyldopa was the major metabolite of administered L-DOPA. Using a dopaminergic cell model, clonal rat phenochromocytoma PC 12h cells, and by microdialysis of the rat striatum it was proved that L-3-O-methyldopa was taken up into monoamine neurons by transport system specific for aromatic L-amino acids and inhibited transport of L-DOPA and other amino acids competitively. L-3-O-Methyldopa depleted allosteric regulation of the biopterin cofactor on activity of tyrosine hydroxylase, the rate-limiting enzyme of catecholamine synthesis. Depletion of the allostery may perturb the buffer action of endogenous L-DOPA synthesis that stabilizes dopamine level in the brain. By these mechanisms L-3-O-methyldopa may reduce clinical effectiveness of administrated L-DOPA and be involved in wearing-off phenomenon. L-DOPA inhibited the activity of tryptophan hydroxylase and thus serotonin synthesis, which may be related to psychiatric side-effects in the patients under L-DOPA therapy.read more
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Reversal learning in Parkinson's disease depends on medication status and outcome valence.
TL;DR: It is shown that dopaminergic medication in PD impairs reversal shifting depending on the motivational valence of unexpected outcomes, and patients ON medication performed as well as patients OFF medication and controls when the reversal was signaled by unexpected reward.
Journal ArticleDOI
The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders.
TL;DR: These studies support a current theory that impaired methylation may occur by different mechanisms in several neurological and psychiatric disorders.
Journal ArticleDOI
Potential mechanisms underlying anxiety and depression in Parkinson's disease: consequences of l-DOPA treatment.
TL;DR: An overview of the clinical characteristics of affective disorders in Parkinson's disease, the utility of animal models for the study of anxiety and depression in PD, and potential mechanisms by which DA loss and subsequent l-DOPA therapy influence monoamine function and concomitant affective symptoms are discussed.
Journal ArticleDOI
Advances in the molecular characterization of tryptophan hydroxylase.
Susan M. Mockus,Kent E. Vrana +1 more
TL;DR: Regulation concepts of TPH activity by posttranslational phosphorylation, kinetic inhibition, and covalent modification, in conjunction with new systems for studying T PH activity are the focus of this article.
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Expanding the repertoire of L-DOPA’s actions: A comprehensive review of its functional neurochemistry
TL;DR: L-DOPA exerts a surprisingly complex pattern of neurochemical effects of much greater scope that mere striatal transformation into DA in spared dopaminergic neurons, and may exert intrinsic receptor-mediated actions independently of DA neurotransmission and can be processed into bioactive metabolites.
References
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A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding
TL;DR: This assay is very reproducible and rapid with the dye binding process virtually complete in approximately 2 min with good color stability for 1 hr with little or no interference from cations such as sodium or potassium nor from carbohydrates such as sucrose.
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The Rat Brain in Stereotaxic Coordinates
George Paxinos,Charles Watson +1 more
TL;DR: This paper presents a meta-analyses of the determinants of earthquake-triggered landsliding in the Czech Republic over a period of 18 months in order to establish a probabilistic framework for estimating the intensity of the earthquake.
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Studies in vivo on the relationship between brain tryptophan, brain 5‐ht synthesis and hyperactivity in rats treated with a monoamine oxidase inhibitor and l‐tryptophan
TL;DR: It is suggested that when monoamine oxidase is inhibited and the rate of 5‐HT synthesis is increased, granular uptake and storage of 5-HT and other rate‐limiting mechanisms for 5‐ht inactivation are unable to prevent 5‐ HT 'spilling over’ to produce hyperactivity.
Journal ArticleDOI
Motor fluctuations in Parkinson's disease: Central pathophysiological mechanisms, part II
TL;DR: It is suggested that postsynaptic modifications, presumably at the receptor level, serve as the major determinant for the increasing difficulty with optimal dose adjustment and motor fluctuations, especially of the on‐off type, which complicate levodopa therapy of patients with advance Parkinson's disease.