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A new function of tetrahydrobiopterin (BH 4 ) was demonstrated  in vitro  in which BH 4  stimulated serotonergic cells to release serotonin (5HT). RBL2H3 cells were pre-loaded with serotonin at 100 μM for 6 hours. The cells were able to release serotonin in response to either 30 mM KCl or 30 nM A23187 up to 2.26±2.06%  (n=15) or 9.75± 1.38% (n=15 ), respectively. On exposure to 6R-L-erythrotetrahydrobiopterin (6RBH 4 ) at 100 μM, the 5HT-Ioaded cells secreted serotonin up to 8.13± 1.43% of the cellular 5HT within 60 min. The effect was a concentration dependent response and the half maximum output was observed at 1 nM or lower. Sepiapterin (&gt; 10 μM) caused minimal release and 6S-L-erythro-tetrahydrobiopterin (6SBH 4 ,≤0 .4 mM) did not cause significant release. The results suggest that the effect of 6RBH 4  was highly stereospecific and that it worked extracellularly.

6R-L-erythro-Tetrahydrobiopterin Triggers Serotonin Release with 5HT-loaded RBL2H3 Cells, a Rat Mast Cell Line