(6R)‐Tetrahydrobiopterin Increases the Activity of Tryptophan Hydroxylase in Rat Raphe Slices

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Abstract
The effects of (6R)‐ and (6S)‐tetrahydrobiopterin (BPH4), tetrahydroneopterin, and 6‐methyltetrahydropterin on the activity of tryptophan hydroxylase were investigated in rat raphe slices. The activity of tryptophan hydroxylase was estimated by measurement of 5‐hydroxytryptophan (5‐HTP) formation under inhibition of aromatic L‐amino acid decarboxylase with use of HPLC‐fluorometric detection. (6R)‐BPH4 (the naturally occurring form) at 42 μM, tetrahydroneopterin at 50 μM, and 6‐methyltetrahydropterin at 100 μM increased tryptophan hydroxylase activity to 350, 145, and 146% of control values, respectively. (6S)‐BPH4, however, had no significant effects on tryptophan hydroxylase activity. These results suggest that tryptophan hydroxylase is subsaturating in vivo for the naturally occurring cofactor, (6R)‐BPH4, and that the concentration of (6R)‐BPH4 may play an important role for the regulation of tryptophan hydroxylase activity in vivo.