Enhancement of Dopamine Release In Vivo from the Rat Striatum by Dialytic Perfusion of 6<i>R</i>‐<scp>l</scp>‐<i>erythro</i>‐5,6,7,8‐Tetrahydrobiopterin

Koshimura, Kunio; Miwa, Soichi; Lee, Ken; Fujiwara, Motohatsu; Watanabe, Yasuyoshi

doi:10.1111/j.1471-4159.1990.tb01974.x

Cited by 93 publications

(74 citation statements)

References 27 publications

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“…As the metabolites, HVA was observed to have the similar change of concentration to DA. These results accorded with early reports [16,29,30]. However, we did not observe obvious increase in DOPAC, 5-HIAA and NE, one possibility is that the concentration of DA or 5-HT has not a decisive influence on them and there are other factors affecting the metabolism of DA to DOPAC and of 5-HT to 5-HIAA.…”

Section: In Vivo Experimentssupporting

confidence: 81%

In Vivo Determination of Tetrahydrobiop- terin and Monoamine Neurotransmitters in Rat Brain by Liquid Chromatography with a Nano Crystalline Mn-Doped Lead Dioxide Film Modified Electrode

Zhang

Wan

et al. 2004

Chromatographia

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The fabrication and application of a novel electrochemical detector (ED) with nano crystalline Mn-doped lead dioxide film chemically modified electrode (CME) for liquid chromatography (LC) were described. The Mn-doped PbO 2 film was characterized by scanning tunnel microscope. The electrochemical behaviors of tetrahydrobiopterin, monoamine neurotransmitters and their metabolites at the CME were investigated by cyclic voltammetry and differential pulse voltammetry. It was found that the CME exhibited efficiently electrocatalytic effect on the current response of the seven analytes and the linear ranges of them were over three orders of magnitude with the detection limits being 5.0 · 10

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Section: In Vivo Experimentssupporting

confidence: 81%

In Vivo Determination of Tetrahydrobiop- terin and Monoamine Neurotransmitters in Rat Brain by Liquid Chromatography with a Nano Crystalline Mn-Doped Lead Dioxide Film Modified Electrode

Zhang

Wan

et al. 2004

Chromatographia

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“…1). It has been proposed that BH 4 may also have cofactorindependent roles (2), including inhibition of cytokine-induced apoptosis (3) and stimulation of dopamine release (4). Cellular levels of BH 4 are regulated by the activity of GTP cyclohydrolase I (GTPCH), the first and rate-limiting enzyme in the BH 4 biosynthetic pathway (5).…”

Section: (R)-5678-tetrahydrobiopterin (Bh 4 )mentioning

confidence: 99%

Involvement of Sphingosine Kinase in TNF-α-stimulated Tetrahydrobiopterin Biosynthesis in C6 Glioma Cells

Vann

Payne

Edsall

et al. 2002

Journal of Biological Chemistry

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In C6 glioma cells, the sphingolipid second messenger ceramide potentiates expression of inducible nitric-oxide synthase (iNOS) induced by tumor necrosis factor ␣ (TNF-␣) without affecting GTP cyclohydrolase I (GT-PCH), the rate-limiting enzyme in the biosynthesis of 6(R)-5,6,7,8-tetrahydrobiopterin (BH 4 ), a cofactor required for iNOS activity. TNF-␣ also stimulates sphingosine kinase, the enzyme that phosphorylates sphingosine to form sphingosine-1-phosphate (SPP), a further metabolite of ceramide. Several clones of C6 cells, expressing widely varying levels of sphingosine kinase, were used to examine the role of SPP in regulation of GTPCH and BH 4 biosynthesis. Overexpression of sphingosine kinase, with concomitant increased endogenous SPP levels, potentiated the effect of TNF-␣ on GTPCH expression and activity and BH 4 biosynthesis. In contrast, enforced expression of sphingosine kinase had no effect on iNOS expression or NO formation. Furthermore, N,N-dimethylsphingosine, a potent sphingosine kinase inhibitor, completely eliminated the increased GTPCH activity and expression induced by TNF-␣. Surprisingly, we found that, although C6 cells can secrete SPP, which is enhanced by TNF-␣, treatment of C6 cells with exogenous SPP or dihydro-SPP had no affect on BH 4 biosynthesis. However, both SPP and dihydro-SPP markedly stimulated ERK 1/2 in C6 cells, which express cell surface SPP receptors. Interestingly, although this ERK activation was blocked by PD98059, which also reduced cellular proliferation induced by enforced expression of sphingosine kinase, PD98059 had no effect on GTPCH activity. Collectively, these results suggest that only intracellularly generated SPP plays a role in regulation of GTPCH and BH 4 levels. 5,6,7, 1 is the obligate cofactor for the aromatic L-amino hydroxylases and is also required for activity of all nitric-oxide synthase isoforms (reviewed in Ref. 1). It has been proposed that BH 4 may also have cofactorindependent roles (2), including inhibition of cytokine-induced apoptosis (3) and stimulation of dopamine release (4). Cellular levels of BH 4 are regulated by the activity of GTP cyclohydrolase I (GTPCH), the first and rate-limiting enzyme in the BH 4 biosynthetic pathway (5). Its expression is increased by proinflammatory cytokines, such as IFN-␥ and TNF-␣, and is coordinately regulated with cytokine-inducible nitric-oxide synthase (iNOS) (6). BH 4 binds to NOS monomers, promoting their dimerization and subsequent activation (7), and recent crystallographic analysis suggests that it may play a direct role in the NOS reaction in a radical form (8). 6(R)-GTPCH, a homodecamer of 30-kDa subunits arranged as two pentamers facing one another (9), catalyzes the rearrangement of GTP to dihydroneopterin triphosphate. This intermediate is then converted to BH 4 in two subsequent reactions catalyzed by 6-pyruvoyltetrahydropterin synthase and sepiapterin reductase, respectively, neither of which are rate-limiting. The signal transduction pathways that regulate induction of GTPCH are not wel...

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“…In separate experiments, this dose of a-MT was found to completely inhibit tyrosine hydroxylation in vivo and hence DA biosynthesis, before and after administration of pteridines (27,30,31). Even after pretreatment with a-MT, 6R-BH 4 induced an increase in DA levels in dialysates, which amounted to 70% of control values in the absence of administration of a-MT ( Figure.…”

Section: Resultsmentioning

confidence: 99%

“…Assay of DA collected in dialysates was, in principle, similar to the method described previously (28,29) but was modified to be suitable for a small volume (27,30,31). After addition of ioo J.lI of 0.1 M perchloric acid containing I mg/ml of sodium bisulfite, I mM EDTA and 20 mg of activated alumina to the dialysate, the pH of the mixture was adjusted to 8.3-8.4 with I M Tris-HCI buffer (pH 8.6) and the mixture was vigorously shaken for 20 min.…”

Section: Assay Of Da In Dialysatesmentioning

confidence: 99%

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6R-L-erythro-5,6,7,8-Tetrahydrobiopterin and Dopamine Release

Miwa

Koshimura

1995

Pteridines

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SummaryWe previously reported that intracerebroventricular administration of 6,7,, a cofactor for aromatic amino acid hydroxylases and nitric oxide synthase, induces an increase in DOPA levels (as an index of DA biosynthesis) and in levels of DA metabolites (as an index of DA release) in the rat brain: the increase in DOPA levels was larger than that of DA metabolites, indicating that 6R-BH 4 enhances DA release. In the present study, we examined the effects of 6R-BH 4 on DA release in vivo from the striatum of male Wistar rats and its mechanism of action using brain microdialysis. When various concentrations of 6R-BJL, 6S-BJL (a diastereoisomer of 6R-BH 4 ) or 6-methyltetrahydropterin (6-MPJL) were added to the perfusion fluid of microdialysis probes, DA levels collected in dialysates increased in a concentration-dependent manner: the 6R-BJL-induced increase was far greater than the increase induced by 6S-BH4 or 6-MPJL. Biopterin had little effect on the DA levels. After i.p. injection of250 mg/kg ofa-methyl-p-tyrosine (a-MT; an inhibitor of tyrosine hydroxylase), most of the 6R-BH 4 -induced increase persisted but the increase induced by 6S-BJL or 6-MPH4 was abolished. The 6R-BH4 -induced increase in DA levels in dialysates was abolished after addition of tetrodotoxin (50 J.1M) to the perfusion fluid, but it persisted after i.p. injection of 100 mg/kg of nomifensine which completely inhibited DA reuptake. The increase in DA levels also persisted after administration of nitric oxide synthase inhibitors. The 6R-BJL-induced increase in DA levels was inhibited by co-administration of 6S-BJL or 6-MPJL. Administration of sepiapterin (an immediate precursor of 6R-BJL) increased tissue levels of reduced biopterin (mainly consisting of 6R-BJL) but not its extracellular levels monitored by brain microdialysis, indicating that it selectively increases the intracellular 6R-BJL levels. In contrast, administration of 6R-BH 4 increased both tissue levels of reduced biopterin and its extracellular levels, indicating that it increases both the intraand extra-cellular 6R-BH 4 leveles. DA levels in dialysates was elevated following administration of sepiaterin (an immediate precursor of 6R-BJL), but the elevation was abolished after pretreatment with a-MT. Furthermore, 6R-BJL increased firing rates of neurons in the dorsal motor nucleus of vagus monitored by a slice patch method. These results suggest that 6R-BJL has a DA releasing action independent of its cofactor for tyrosine hydroxylase and nitric oxide synthase, which is mediated by a specific recognition site for 6R-BH4 on DA neurons or related cells.

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Enhancement of Dopamine Release In Vivo from the Rat Striatum by Dialytic Perfusion of 6R‐l‐erythro‐5,6,7,8‐Tetrahydrobiopterin

Cited by 93 publications

References 27 publications

In Vivo Determination of Tetrahydrobiop- terin and Monoamine Neurotransmitters in Rat Brain by Liquid Chromatography with a Nano Crystalline Mn-Doped Lead Dioxide Film Modified Electrode

In Vivo Determination of Tetrahydrobiop- terin and Monoamine Neurotransmitters in Rat Brain by Liquid Chromatography with a Nano Crystalline Mn-Doped Lead Dioxide Film Modified Electrode

Involvement of Sphingosine Kinase in TNF-α-stimulated Tetrahydrobiopterin Biosynthesis in C6 Glioma Cells

6R-L-erythro-5,6,7,8-Tetrahydrobiopterin and Dopamine Release

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