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 μM. At these concentrations 6-MPH4 did not have any effect on dopamine release. Presence of Nω-Nitro-l-arginine methyl ester (l-NAME, 200 μM), a nitric oxide synthase inhibitor, but not of α-methyl-ρ-tyrosine (α-MPT, 100 μM), a tyrosine hydroxylase inhibitor, blocked l-DOPA release induced by 6-MPH4 (200 μM). Also, the addition to the incubation medium of melatonin (MEL, 300 μM), which is a scavenger of NO and other free radicals, blocked the l-DOPA release induced by 6-MPH4 (200 μM) but this effect did not occur with the addition of the peroxynitrite scavenger uric acid (UA, 300 μM). Sodium nitroprusside (SNP, 100 μM), a NO generator and l-DOPA releaser as previously reported, potentiated the l-DOPA releasing effect of 6-MPH4 (200 μM) 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.