Tetrahydrobiopterin stimulates L-DOPA release from striatal tissue.
In the present study we have analyzed the effect of tetrahydrobiopterin (BH4) essential cofactor for tyrosine hydroxylase and nitric oxide synthase, on the 3,4-dihydroxyphenylalanine (L-DOPA) release from in vitro incubated striatal tissue. dl-6-methyl-5,6,7,8 tetrahydropterine (6-MPH4)-stimulated L-DOPA release in a concentration-dependent manner in the range from 25 to 100 microM. At these concentrations 6-MPH4 did not have any effect on dopamine release. Presence of Nomega-Nitro-L-arginine methyl ester (L-NAME, 200 microM), a nitric oxide synthase inhibitor, but not of alpha-methyl-rho-tyrosine (alpha-MPT, 100 microM), a tyrosine hydroxylase inhibitor, blocked L-DOPA release induced by 6-MPH4 (200 microM). Also, the addition to the incubation medium of melatonin (MEL, 300 microM), which is a scavenger of NO and other free radicals, blocked the L-DOPA release induced by 6-MPH4 (200 microM) but this effect did not occur with the addition of the peroxynitrite scavenger uric acid (UA, 300 microM). Sodium nitroprusside (SNP, 100 muM), a NO generator and l-DOPA releaser as previously reported, potentiated the L-DOPA releasing effect of 6-MPH4 (200 microM) which was also blocked by melatonin. In summary 6-MPH4 stimulates L-DOPA release from striatal fragments incubated in vitro by a mechanism which involves NO or other free radicals derived from NO but not peroxynitrite.
Abreu-González
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P
Department of Physiology, University of La Laguna. 38320 Tenerife, Spain.
González-Hernández
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Afonso-Oramas
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D
Cruz-Muros
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Barroso-Chinea
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González
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MC
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D007980:Levodopa / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D011622:Pterins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019805:alpha-Methyltyrosine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D020030:Nitric Oxide Donors; D011622:Pterins; D009599:Nitroprusside; D001708:Biopterins; D007980:Levodopa; D019805:alpha-Methyltyrosine; C017523:6-methyltetrahydropterin; D019001:Nitric Oxide Synthase; D014446:Tyrosine 3-Monooxygenase; C003402:sapropterin; D008550:Melatonin; D019331:NG-Nitroarginine Methyl Ester