Oxidative decarboxylation of salsolinol-1-carboxylic acid to 1,2-dehydrosalsolinol: Evidence for exclusive catalysis by particulate factors in rat kidney

Collins, Michael A.; Cheng, B

doi:10.1016/0003-9861(88)90616-9

Cited by 16 publications

(6 citation statements)

References 28 publications

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“…The significance of these higher (hypothalamic) concentrations early in the EtOH regimen remains to be determined. Initial hypothalamic mechanisms that regulate drinking (Amit and Stern, 197 1;Meyers et al, 1985) might be affected by the sTIQs, or the sTIQs may serve to initiate some aspect of neuronal degeneration, possibly, in the 1-carboxylated cases, via formation of 3,4-dihydroisoquinolines (Collins and Cheng, 1988). However, it is difficult to envision the sTIQs as part of a general ongoing mechanism of damage as originally postulated (Collins, 1982), because their concentrations were not significantly increased in the striatum, where nerve terminal loss occurred after EtOH ingestion for nearly 6 months, or in the circulation at either exposure time.…”

Section: Discussionmentioning

confidence: 99%

“…For HPLC, aliquots (1 0-20 pl) of the acid supernatants were removed, 3,4-dihydroxybenzylamine (DHBA, internal standard) was added, and the sample was diluted for quantitation of DA, serotonin (5-HT), and their acid metabolites. The reversed phase HPLC system and conditions were described previously by Cheng et al (1987) and Collins and Cheng ( 1988). Aliquots also were taken for protein determination according to Lowry et al (1951).…”

Section: Methodsmentioning

confidence: 99%

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

Collins

Ung-Chhun

Cheng

et al. 1990

Journal of Neurochemistry

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

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

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“…Traces of 1-methyl-3,4-dihydro-6,7-isoquinolinediol (1,2-dehydroSal) have been found in extracts of human brain (Ung-Chhun et al, 1985), but the compound could have resulted from 1-carboxy-Sal as an artefact due to air oxidation after death. Decarboxylation of 1-carboxy-Sal by incubation with rat tissues, including brain, was found to result in the formation of 1,2-dehydroSal only (Collins and Cheng, 1988). No Sal was detected, even with added NADPH.…”

Section: Discussionmentioning

confidence: 93%

Enantiomeric composition of urinary salsolinol in Parkinsonian patients after Madopar

Dostert

Benedetti

Dordain

et al. 1989

J Neural Transm Gen Sect

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Urinary salsolinol output had been shown to be lower in Parkinsonian patients than in controls and to increase largely after L-dopa therapy. It had also been established that the R enantiomer of salsolinol is either the predominant or the sole enantiomer present in the urine of healthy subjects. When Madopar was administered to Parkinsonians, the enantiomeric composition of urinary salsolinol showed an S/R ratio around 1. Considering brain and plasma concentrations in dopamine, acetaldehyde and pyruvate, it is suggested that, under physiological conditions, urinary salsolinol should have a central origin in humans. Conversely, urinary salsolinol in Madopar-treated Parkinsonian patients might be predominantly formed at the periphery.

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“…The fact that salsolinol was not found in urine of subject 1 after administration of Madopar shows that there is no alternative pathway for salsolinol formation in humans, and also that salsolinol does not derive from direct decarboxylation of 1-carboxy-salsolinol. The inability of subject 1 to reduce 1,2-dehydrosalsolinol has to be considered with regard to the recent results reported by Collins and Cheng (1988), who found that incubation of 1-carboxy-salsolinol with rat liver or whole brain homogenates led to the formation of 1,2-dehydrosalsolinol only; no traces of salsolinol were found, even with added NADPH. 1,2-Dehydrosalsolinol has been reported to be a potent inhibitor of catechol-O-methyltransferase (Cheng et al, 1987) Its increased formation after administration of Madopar might contribute to the beneficial effects of L-dopa therapy by inhibiting one of the catabolic pathways of DA.…”

Section: Discussionmentioning

confidence: 99%

Biosynthesis of salsolinol, a tetrahydroisoquinoline alkaloid, in healthy subjects

Dostert

Benedetti

Bellotti

et al. 1990

J. Neural Transmission

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The R enantiomer of salsolinol was detected in the urine of two out of six healthy subjects, whereas 1,2-dehydrosalsolinol was present in the urine of all the subjects. (S)-salsolinol was never detected. Administration of Madopar for 7 days resulted in the presence of large amounts of (R)- and (S)-salsolinol in the urine of five out of the six subjects, the urinary excretion of 1,2-dehydrosalsolinol being generally not markedly increased. The presence of 1,2-dehydrosalsolinol in urine suggests that the biosynthesis of salsolinol in healthy volunteers should occur by condensation of dopamine with pyruvic acid, in keeping with Hahn's hypothesis. The absence of salsolinol in the urine of one subject after Madopar administration seems to indicate that the biological system(s) involved in the reduction of the C = N bond in 1,2-dehydrosalsolinol can be missing or not, or poorly, functional in some individuals, and suggests that there is no alternative pathway for the formation of salsolinol in healthy volunteers.

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Oxidative decarboxylation of salsolinol-1-carboxylic acid to 1,2-dehydrosalsolinol: Evidence for exclusive catalysis by particulate factors in rat kidney

Cited by 16 publications

References 28 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

Enantiomeric composition of urinary salsolinol in Parkinsonian patients after Madopar

Biosynthesis of salsolinol, a tetrahydroisoquinoline alkaloid, in healthy subjects

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