Presence of free, sulfate and glucuronide conjugated 3-methoxy-4-hydroxyphenylglycol (MHPG) in human brain, cerebrospinal fluid and plasma

doi:10.1016/0006-8993(77)90626-6

Brain Research

Volume 125, Issue 2, 15 April 1977, Pages 333-339

https://doi.org/10.1016/0006-8993(77)90626-6 Get rights and content

Abstract

The concentration of the free, glucuronide and the sulfate conjugated forms of 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured in human plasma, cerebrospinal fluid (CSF) and brain by mass fragmentography.

All three forms of MHPG were detected in the media analyzed. Free MHPG was found to be the predominant form in both the brain and the CSF. The sulfate conjugate of MHPG constitutes about 15% of the total MHPG in the CSF while in the brain the percentage varies between 30% in the hypothalamus and cortex and 80% in the substantia nigra.

The concentration of the glucuronide conjugate of MHPG measured in the brain and CSF represents about 5% of the total MHPG concentration.

In the plasma free MHPG and its glucuronide and sulfate conjugates are present in about equal concentrations.

The relative concentrations of the three forms of MHPG measured in plasma, CSF and brain were compared with their concentrations in the urine from previously published results⁹. From this comparison the diagnostic significance of each of the three forms of MHPG in the clinical assessment of central norepinephrine metabolism is discussed.

Reference (12)

ArmstrongM.D. et al.
3-Methoxy-4-hydroxy-D-mandelic acid, or urinary metabolite of norepinephrine
Biochim. biophys. Acta (Amst.)
(1957)
AxelrodJ. et al.
3-Methoxy-4-hydroxyphenylglycol sulfate, a new metabolite of epinephrine and norepinephrine
Biochim. biophys. Acta (Amst.)
(1959)
JimersonD.C. et al.
Central noradrenergic function in man: vanillylmandelic acid in CSF
Brain Research
(1975)
KaroumF. et al.
Vanilmandelic acid (VMA), free and conjugated 3-methoxy-4-hydroxyphenylglycol (MHPG) in human ventricular fluid
Clin. chim. Acta
(1975)
KaroumF. et al.
Urinary excretion of 4-hydroxy-3-methoxyphenylglycol and 4-hydroxy-3-methoxyphenyl ethanol in man and rat
Clin. chim. Acta
(1973)
SchanbergS.M. et al.
Metabolism of normetanephrine-H³ in rat brain-identification of conjugated 3-methoxy-4-hydroxyphenylglycol as the major metabolite
Biochem. Pharmacol.
(1968)

There are more references available in the full text version of this article.

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Presence of free, sulfate and glucuronide conjugated 3-methoxy-4-hydroxyphenylglycol (MHPG) in human brain, cerebrospinal fluid and plasma

Abstract

Biochim. biophys. Acta (Amst.)

Biochim. biophys. Acta (Amst.)

Brain Research

Clin. chim. Acta

Clin. chim. Acta

Biochem. Pharmacol.