Tetrahydrobiopterin uptake into rat brain synaptosomes, cultured PC12 cells, and rat striatum.
The uptake of (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4) was investigated in rat brain synaptosomes, cultured rat pheochromocytoma (PC12) cells, and rat striatum (control and depleted of dopamine neurons) following peripheral administration. A linear, non-saturable, concentration-dependent intracellular accumulation was observed when BH4 was added to either synaptosomes or PC12 cells. The uptake of BH4, in contrast to that of serotonin uptake into synaptosomes or norepinephrine (NE) uptake into PC12 cells, was not dependent on glucose or extracellular sodium. Stimulation of tryptophan hydroxylation in synaptosomes by incubation with 5 microM tryptophan (which increases utilization of BH4 in serotonergic cells) did not alter BH4 uptake. In rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of dopamine neurons, BH4 uptake was the same in control and lesioned striatum following peripheral administration. These results indicate that neurons and PC12 cells do not appear to have a specific membrane carrier for BH4 and that BH4 uptake into cells is due to passive diffusion.
Anastasiadis
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PZ
William T. Gossett Neurology Laboratories, Henry Ford Hospital, Detroit, MI 48207.
Kuhn
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DM
Levine
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RA
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism*
D001708:Biopterins; D012701:Serotonin; C003402:sapropterin; D009638:Norepinephrine