Asymmetric uptake of sepiapterin and 7,8-dihydrobiopterin as a gateway of the salvage pathway of tetrahydrobiopterin biosynthesis from the lumenal surface of rat endothelial cells

Rat aortic endothelial cells were cultured on a porous membrane to form a monolayer sheet. They efficiently accumulated tetrahydrobiopterin (BH(4)) by uptake of sepiapterin but did so only moderately by uptake of dihydrobiopterin. The endothelial cell sheet preferentially took up the pterins from the apical side. Accordingly, a dense accumulation of ENT2-like immunoreactivity was visualized on the apical surface of the cell sheet. The findings suggest that vascular endothelial cells receive BH(4) precursors directly from the blood stream rather than from ablumenal tissues.