Studies on the activity of L-threo-3,4-dihydroxyphenylserine (L-DOPS) as a catecholamine precursor in the brain. Comparison with that of L-dopa.
L-Threo-3,4-dihydroxyphenylserine (L-DOPS) was compared with L-3,4-dihydroxyphenylalanine (L-DOPA) with respect to their activities as central amine precursors. The apparent Km value (the substrate affinity) of L-DOPS for aromatic L-amino acid decarboxylase was nearly equal to that of L-DOPA, whereas the vmax value (the rate of decarboxylation) of L-DOPS was much smaller than that of L-DOPA, the penetration of L-DOPS into the brain through the blood-brain barrier was found to be smaller (about one-fourth) than that of L-DOPA but, for an amine precursor, it was still substantial. Unlike L-DOPA, L-DOPS did not cause a marked accumulation of norepinephrine (NE), the corresponding catecholamine in the brain, but nialamide, a monoamine oxidase inhibitor significantly enhanced the L-DOPS-induced rise of NE. Moreover, the brain concentration of 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG), the principal end metabolite of NE, was increased markedly by L-DOPS. These results suggest that L-DOPS may act as an NE precursor in the brain and activate NE neurons by increasing the turnover rate of NE.
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D015103:Droxidopa / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D007980:Levodopa / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D051379:Mice; D009526:Nialamide / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012694:Serine / Q000031:analogs & derivatives*; D013379:Substrate Specificity
D002395:Catecholamines; D011498:Protein Precursors; D012694:Serine; D007980:Levodopa; D008734:Methoxyhydroxyphenylglycol; D001142:Aromatic-L-Amino-Acid Decarboxylases; D015103:Droxidopa; D009526:Nialamide; D004298:Dopamine; D009638:Norepinephrine