Plasticity of extrapyramidal dopamine system in Parkinson's disease - A postmortem study

Antkiewicz-Michaluk, L; Krygowska‐Wajs, Anna; Michaluk, Jerzy; Romańska, Irena; Szczudlik, Andrzej; Vetulani, Jerzy

doi:10.1002/(sici)1520-6769(199909/10)25:2<97::aid-nrc5>3.0.co;2-k

Cited by 4 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1986). Because of this, it is especially vulnerable as small damage may lead to irreparable functional deficits, although the system is capable of substantial compensatory adaptations (Antkiewicz‐Michaluk et al . 1999).…”

Section: Discussionmentioning

confidence: 99%

Different action on dopamine catabolic pathways of two endogenous 1,2,3,4‐tetrahydroisoquinolines with similar antidopaminergic properties

Antkiewicz-Michaluk¹,

Michaluk²,

Mokrosz³

et al. 2001

Journal of Neurochemistry

Self Cite

View full text Add to dashboard Cite

The effect of single and multiple 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) and 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ) administration on concentrations of dopamine and its metabolites: homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3MT) in three brain areas was studied HPLC with electrochemical detection in Wistar rats. The rate of dopamine catabolism in the striatum along the N-oxidative and O-methylation pathways was assessed by calculation of the ratio of appropriate metabolites to dopamine concentration. In addition, the spontaneous and apomorphine-stimulated locomotor activity, and muscle rigidity was studied after acute administration of 1MeTIQ and 1BnTIQ. We have found that 1MeTIQ did not change the level of dopamine and HVA in all investigated structures both after a single and chronic administration. However, the levels of intermediary dopamine metabolites, DOPAC and 3MT, were distinctly affected. The level of DOPAC was strongly depressed (by 60±70%) while the level of extraneuronal matabolite 3MT was signi®cantly elevated (by 170±200%). In contrast to 1MeTIQ, 1BnTIQ depressed the level of dopamine (by approximately 60%) and increased the level of total metabolite, HVA, (by 40%) especially in the striatum, but the levels of DOPAC and 3MT remained unchanged. The paper has shown that 1MeTIQ and 1BnTIQ produced different effects on dopamine catabolism. Potential neuroprotective compound 1MeTIQ did not change the rate of total dopamine catabolism, it strongly inhibited the monoamine oxidase (MAO)-dependent catabolic pathway and signi®cantly activated the catechol-O-methyltransferase (COMT)-dependent O-methylation. In contrast 1BnTIQ, a compound with potential neurotoxic activity, produced the signi®cant increase of the rate of dopamine metabolism with strong activation of the oxidative MAO-dependent catabolic pathway. Interestingly, both compounds produced similar antidopaminergic functional effects: antagonism of apomorphine hyperactivity and induction of muscle rigidity. The results may explain the biochemical basis of the neuroprotective and of the neurotoxic properties endogenous brain tetrahydroisoquinoline derivatives.

show abstract

Section: Discussionmentioning

confidence: 99%

Different action on dopamine catabolic pathways of two endogenous 1,2,3,4‐tetrahydroisoquinolines with similar antidopaminergic properties

Antkiewicz-Michaluk¹,

Michaluk²,

Mokrosz³

et al. 2001

Journal of Neurochemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Radioligand binding studies were carried out on rat cortex according to the published procedures using [ 3 H]prazosin (26 Ci/mmol, NEN Chemicals) and [ 3 H]aminoclonidine (40.2 Ci/mmol, NEN Chemicals) for α1-AR [10] and α2-AR [11] , respectively. The Ki values were determined on the basis of at Notes A series of benzolactam derivatives has been evaluated for their affinity for α1 and α2-adrenoreceptors.…”

Section: Binding Experimentsmentioning

confidence: 99%

Benzolactam Derivatives and Their Affinity for α1- and α2- Adrenoreceptors

Mokrosz

Charakchieva-Minol

Kowalski

2001

Arch. Pharm. Pharm. Med. Chem.

View full text Add to dashboard Cite

A series of benzolactam derivatives has been evaluated for their affinity for α1 and α2‐adrenoreceptors. The influence of terminal amine and amide fragments on the affinity and selectivity has been investigated. It has been found that derivatives containg 1,2,3,4‐tetrahydroisoquinoline (THIQ) as the basic component can form potent α1 and/or α2 ligands, and that their α1/α2 selectivity depends on the benzolactam fragment.

show abstract

1-Benzyl-1,2,3,4-Tetrahydroisoquinoline, an Endogenous Parkinsonism-Inducing Toxin, Strongly Potentiates MAO-Dependent Dopamine Oxidation and Impairs Dopamine Release: Ex vivo and In vivo Neurochemical Studies

2009

Self Cite

View full text Add to dashboard Cite

1-Benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ), an endogenous neurotoxin, is known to cause a parkinsonism-like syndrome in rodents and primates. In this study we evaluated the effects of single and multiple 1BnTIQ (50 mg/kg i.p.) administration on the concentrations of dopamine, serotonin, and respective metabolites (homovanillic acid, HVA; 3,4-dihydroxyphenylacetic acid, DOPAC; 3-methoxytyramine, 3-MT; and 5-hydroxyindolacetic acid, 5-HIAA), in substantia nigra, striatum (STR), and nucleus accumbens of Wistar rats. In addition, the effect of 1BnTIQ on locomotor activity and dopamine release in vivo was also estimated in rat STR. In a behavioral study, acute administration of 1BnTIQ (50 mg/kg i.p.) produced a significant decrease in exploratory locomotor activity. A high-performance liquid chromatography with electrochemical detection ex vivo study showed that a single injection of 1BnTIQ produced a dramatic fall in the dopamine concentration in the noted brain regions (approximately 65%; P < 0.01), but not in striatal serotonin. Moreover, 1BnTIQ reduced the content of the extraneuronal dopamine metabolite 3-MT by 70% (P < 0.01). Conversely, levels of DOPAC, HVA, and 5-HIAA were elevated by 220, 320, and 185%, respectively (P < 0.01). Interestingly, multiple 1BnTIQ treatments (50 mg/kg/day i.p. x 10 days) resulted in development of tolerance to its dopamine depressing effect, while the impairment of dopamine synthesis was persisted. An in vivo microdialysis study demonstrated that 1BnTIQ (50 mg/kg i.p.) produced a profound and long-lasting decrease in extraneuronal striatal dopamine. Concurrently, however, DOPAC and HVA were elevated. This comparison between ex vivo and in vivo effects of 1BnTIQ provides greater insight into the neurotoxic actions of 1BnTIQ specific to dopamine neurons. 1BnTIQ neurotoxicity may be related to an impairment of dopamine storage, leading to a fall in intraneuronal dopamine and enhanced dopamine catabolism through a monoamine oxidize-dependent oxidative pathway that results in free radical production and ultimate cell death. Because 1BnTIQ is an endogenous compound, it may be one of the factors responsible for idiopathic Parkinson's disease.

show abstract

Plasticity of extrapyramidal dopamine system in Parkinson's disease - A postmortem study

Cited by 4 publications

References 0 publications

Different action on dopamine catabolic pathways of two endogenous 1,2,3,4‐tetrahydroisoquinolines with similar antidopaminergic properties

Different action on dopamine catabolic pathways of two endogenous 1,2,3,4‐tetrahydroisoquinolines with similar antidopaminergic properties

Benzolactam Derivatives and Their Affinity for α1- and α2- Adrenoreceptors

1-Benzyl-1,2,3,4-Tetrahydroisoquinoline, an Endogenous Parkinsonism-Inducing Toxin, Strongly Potentiates MAO-Dependent Dopamine Oxidation and Impairs Dopamine Release: Ex vivo and In vivo Neurochemical Studies

Contact Info

Product

Resources

About