Interspecies differences in the metabolism of brain norepinephrine to glycol metabolites

Using a highly sensitive and specific gas chromatography-mass spectrometric assay, the glycol metabolites of norepinephrine (NE), 3,4-dihydroxyphenylethyleneglycol (DHPG) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) were determined simultaneously in brain and body fluids of several mammalian species, including humans. Highest molar ratios of DHPG to MHPG were found in rat brain (1.20), a species in which these glycol metabolites were primarily conjugated. In mouse, guinea pig, hamster, monkey, and human brain, DHPG and MHPG were mostly unconjugated, and DHPG concentrations were about 30–60% of the respective MHPG levels. In dog cortex, MHPG occurred predominantly as conjugates, whereas DHPG could only be detected in its unconjugated form. In all species studies, highest DHPG and MHPG concentrations occurred in hypothalamus followed, in general, by midbrain and brainstem whereas cerebral cortex, caudate and cerebellum had the lowest values. These results demonstrate substantial differences in the degree of conjugation and relative abundance of brain DHPG compared to MHPG between the rat and other animal species studied.