Effect of L-threo-3,4-dihydroxyphenylserine(L-threo-DOPS) on brain and serum MHPG levels in mice: evidence for NE formation in CNS.
Effects of L-threo-DOPS on brain and serum concentrations of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), a major metabolite of 1-norepinephrine(NE) were studied in mice. An intraperitoneal(i.p.) injection of L-threo-DOPS markedly increased both serum and brain MHPG levels in mice. This increase in the brain was dose-dependent at doses up to 800 mg/kg, and lasted for 4 h or more. Though the increase in serum total-MHPG was 3-4 times greater than that in brain MHPG, the decline was rapid as compared with the case of brain MHPG. The L-threo-DOPS-induced increase in MHPG was inhibited by i.p. pretreatment with benserazide, a peripheral decarboxylase inhibitor, in both serum and brain. This inhibition in the brain, however, was observed at about 20 times higher doses of benserazide than that in serum. On the contrary, an intracerebroventricular(i.c.v.) injection of benserazide inhibited the increase in brain MHPG to about the same degree as that in serum MHPG. These results suggest that the L-threo-DOPS-induced increase in brain MHPG is not likely to originate in peripheral organs including the brain capillary, and that L-threo-DOPS can be converted to NE by aromatic L-amino acid decarboxylase(AADC) in the brain parenchyma.
D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015103:Droxidopa / Q000494:pharmacology*; D006018:Glycols / Q000032:analysis*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000032:analysis*; D051379:Mice; D009638:Norepinephrine / Q000096:biosynthesis*; D012694:Serine / Q000031:analogs & derivatives*
D006018:Glycols; D012694:Serine; D008734:Methoxyhydroxyphenylglycol; D001545:Benserazide; D015103:Droxidopa; D009638:Norepinephrine