PT - JOURNAL ARTICLE AU - J Bartholini AU - J Constantinidis AU - M Puig AU - R Tissot AU - A Pletscher TI - The stereoisomers of 3,4-dihydroxyphenylserine as precursors of norepinephrine. DP - 1975 May 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 523--532 VI - 193 IP - 2 4099 - http://jpet.aspetjournals.org/content/193/2/523.short 4100 - http://jpet.aspetjournals.org/content/193/2/523.full SO - J Pharmacol Exp Ther1975 May 01; 193 AB - The action of the four stereoisomers of 3,4-dihydroxyphenylserine (DOPS) on the monoamine content of brain and heart was investigated with biochemical and histochemical methods. The (+)-erythro-DOPS (50-250 mg/kg i.p.), due to its alphaS configuration, was readily decarboxylated in vivo leading to an accumulation of norepinephrine (NE) in brain and heart. The amino probably corresponded to the unnatural (+) form since the amino acid shows betaS configuration. The NE was located in brain regions rich in noradrenergic (hypothalamus, locus ceruleus), dopaminergic (neostriatum, substantia nigra) and 5-hydroxytryptaminergic (raph'e nuclei) neurons. In addition, (+)-erythro-DOPS decreased the level of endogenous 5-hydroxytryptamine and dopamine and increased that of 5-hydroxyindoleacetic and homovanillic acid in the brain indicating a displacement of 5-hydroxytryptamine and dopamine, respectively, from their storage sites. Inhibitors of extracerebral decarboxylase (benserazid and carbidopa) diminished the (+)-erythro-DOPS-induced increase in cerebral NE by inhibiting the decarboxylation of the amino acid in the walls of the brain capillaries. The (-)-threo-DOPS, which also show alphaS configuration, was decarboxylated too, leading to a rise in cardiac NE. The amine was likely to correspond to the natural(-)-isomer since (-)-threo-DOPS has betaR configuration. This increase in NE lasted much longer than that caused by (+)-erythro-DOPS. In the brain, the accumulation of NE was negligible after i.p. administration of (-)-threo-DOPS but marked after injection of the isomer into a cerebral ventricle indicating a poor penetration of (-)-threo-DOPS through the blood-brain barrier. High doses (500 and 1000 mg/kg i.p.) of (-)-erythro- and (+)-threo-DOPS caused only a slight increase in cerebral and cardiac NE since, due to their alphaR configuration, they were probably not decarboxylated to a major extent. In conclusion, (+)-NE formed from (+)-erythro-DOPS probably accumulates in the storage sites of the endogenous monoamines where it might function as a false neurotransmitter.