Effect of acute ethanol administration on brain levels of tetrahydropapaveroline in L‐dopa‐treated rats

Cashaw, Jesse L.; Geraghty, Carol A.; McLaughlin, Barbara R.; Davis, Virginia E.

doi:10.1002/jnr.490180318

Cited by 27 publications

(5 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, in reconsidering the total chow DOPA estimates of Hoeldtke et al (19721, we may have underestimated the DOPA supplement in our EtOH diet study. Parenthetically, a large dose of L-DOPA in EtOH-treated rats was effective in raising the brain concentration of another (complex) DA-derived TIQ, tetrahydropapaveroline, to a detectable level (Cashaw et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

Brain and Plasma Tetrahydroisoquinolines in Rats: Effects of Chronic Ethanol Intake and Diet

Collins

Ung-Chhun

Cheng

et al. 1990

Journal of Neurochemistry

View full text Add to dashboard Cite

Brain concentrations of salsolinol (SAL), a simple tetrahydroisoquinoline (sTIQ) condensation product of dopamine (DA) and acetaldehyde, are reported to increase in chow-fed rats drinking ethanol/H2O ad libitum. However, our analyses showed that rat chow contains traces of SAL and, as previously reported, appreciable 3,4-dihydroxyphenylalanine (DOPA), a sTIQ precursor. To examine the effect of consumption of ethanol in a DOPA- and SAL-free diet on endogenous sTIQs, we analyzed two brain regions and blood plasma of rats undergoing prolonged intake (3 weeks and 23 weeks) of liquid diet containing 6.6% ethanol or isocaloric carbohydrate. SAL and three other DA-related sTIQs were quantitated using capillary gas chromatography/mass spectrometry in the selected ion mode with deuterated standards. In accord with studies on ethanol/chow-fed rats, sTIQ concentrations in hypothalamus were elevated after 3 weeks of ethanol, although after 23 weeks, hypothalamic sTIQs were either unchanged or reduced (O-methylated SAL). Furthermore, sTIQ concentrations in corpus striatum and, with one exception, plasma were not altered by ethanol ingestion for either duration. (However, 23 weeks of ethanol intake significantly reduced the striatal concentrations of DA and its acid metabolite, presumably reflecting neurotoxicity.) Reasoning that DOPA in diet might underlie the reported ethanol-dependent increases in striatal sTIQs, we found that L-DOPA supplementation (500 micrograms/rat/day) of EtOH/liquid diet-fed rats for 13 weeks tended to increase striatal SAL. Overall, the data indicate that elevations in endogenous sTIQ concentrations due to prolonged ethanol intake depend on the brain region, duration of intake, and even associated dietary constituents. In that regard, the higher striatal SAL concentrations in rats drinking ethanol ad libitum could have been facilitated by DOPA and perhaps SAL consumed in lab chow.

show abstract

Section: Discussionmentioning

confidence: 99%

Brain and Plasma Tetrahydroisoquinolines in Rats: Effects of Chronic Ethanol Intake and Diet

Collins

Ung-Chhun

Cheng

et al. 1990

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…Interestingly, the reports cited above are also confirmatory of a 1987 preclinical study demonstrating dramatic increases in rat brain concentrations of THP subsequent to peripheral co-administration of L-DOPA and ethanol [44]. Despite an excessively high concentration of ethanol (3 g/kg) that was administrated via the intraperitoneal route, it is apparent that a rapid synthesis of THP was accomplished over a 1–2 hour time frame.…”

Section: Biological Signficance Of Tetrahydropapaveroline As a Periphmentioning

confidence: 60%

Parkinson’s disease, L-DOPA, and endogenous morphine: A revisit

et al. 2012

View full text Add to dashboard Cite

SummaryClinical observations stemming from widespread employment of restorative L-3,4-dihydroxyphenylalanine (L-DOPA) therapy for management of dyskinesia in Parkinson’s Disease (PD) patients implicate a regulatory role for endogenous morphine in central nervous system dopamine neurotransmission. Reciprocally, it appears that restorative L-DOPA administration has provided us with a compelling in vivo pharmacological model for targeting peripheral sites involved in endogenous morphine expression in human subjects. The biological activities underlying endogenous morphine expression and its interaction with its major precursor dopamine strongly suggest that endogenous morphine systems are reciprocally dysregulated in PD. These critical issues are examined from historical and current perspectives within our short review.

show abstract

“…In this way, the high concentrations of dopamine resulting from the administration of L-dopa, together with the high concentrations of 3,4-dihydroxyphenylacetaldehyde resulting from the inhibition of the aldehyde dehydrogenase, may increase brain concentrations of THP. In addition, it seems interesting to note at this point that brain levels of THP in rats treated with L-dopa are markedly increased when ethanol is coadministered with L-dopa [15], a circumstance that may also be present in patients with Parkinson's disease. Figure 1 illustrates the pathways suggested for THP formation from L-dopa.…”

Section: Introductionmentioning

confidence: 97%

Study on the ability of 1,2,3,4‐tetrahydropapaveroline to cause oxidative stress: Mechanisms and potential implications in relation to parkinson's disease

Soto‐Otero¹,

Sanmartín-Suárez²,

Sánchez-Iglesias³

et al. 2006

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Tetrahydropapaveroline (THP) is a compound derived from dopamine monoamine oxidase-mediated metabolism, particularly present in the brain of parkinsonian patients receiving L-dopa therapy, and is capable of causing dopaminergic neurodegeneration. The aim of this work was to evaluate the potential of THP to cause oxidative stress on mitochondrial preparations and to gain insight into the molecular mechanisms responsible for its neurotoxicity. Our data show that THP autoxidation occurs with a continuous generation of hydroxyl radicals (*OH) and without the involvement of the Fenton reaction. The presence of ascorbate enhances this process by establishing a redox cycle, which regenerates THP from its quinolic forms. It has been shown that the production of *OH is not affected by the presence of either ferrous or ferric iron. Although THP does not affect lipid peroxidation, it is capable of reducing the high levels of thiobarbituric acid-reactive substances obtained in the presence of ascorbate and/or iron. However, THP autoxidation in the presence of ascorbate causes both an increase in protein carbonyl content and a reduction in protein-free thiol content. THP also increases protein carbonyl content when the autoxidation occurs in the presence of iron. The remarkable role played by ascorbate in the production of oxidative stress by THP autoxidation is of particular interest.

show abstract

Effect of acute ethanol administration on brain levels of tetrahydropapaveroline in L‐dopa‐treated rats

Cited by 27 publications

References 19 publications

Brain and Plasma Tetrahydroisoquinolines in Rats: Effects of Chronic Ethanol Intake and Diet

Brain and Plasma Tetrahydroisoquinolines in Rats: Effects of Chronic Ethanol Intake and Diet

Parkinson’s disease, L-DOPA, and endogenous morphine: A revisit

Study on the ability of 1,2,3,4‐tetrahydropapaveroline to cause oxidative stress: Mechanisms and potential implications in relation to parkinson's disease

Contact Info

Product

Resources

About