Effect of tetrahydrobiopterin on dopamine release from PC12 cells

We previously reported that tetrahydrobiopterin (6R-BH4), a natural cofacto r for aromatic amino acid hydroxylases and nitric oxide synthase, stimulate s dopamine release from rat striatum independently of its cofactor activity . In the present study, we further investigated the effect of 6R-BH4 on dop amine release using differentiated PC12 cells. In PC12 cells, GR-BH4 (10 mu M and 30 mu M) stimulated dopamine release in a dose-related manner, which was persisted in the presence of alpha-methyl-p-tyrosine (1 mM) or L-nitro -arginine methyl ester (100 mu M). Dopamine release from PC12 cells was not stimulated by 6S-BH4, a diastereoisomer of 6R-BH4, or sepiapterin, a precu rsor of 6R-BH4. These results were consistent with the effects of 6R-BH4 on dopamine release from rat striatum. Dopamine release induced by 6R-BH4 was inhibited by nicardipine (1 mu M), suggesting that 6R-BH4-induced dopamine release is mediated by Ca2+ channel activation. Ca-45(2+) uptake and intra cellular Ca2+ concentration in PC12 cells were increased by 6R-BH4. Membran e potential of PC12 cells was depolarized by 6R-BH4. These data taken toget her suggest that 6R-BH4 stimulates dopamine release from PC12 cells by indu cing membrane depolarization which is a trigger for Ca2+ channel activation .