Summary
Measurement of total (free + conjugated) 3 methoxy-4-hydroxyphenylglycol (MHPG) in urine has long been used to assess the metabolism of central norepinephrine (NE). However, available data indicate that total MHPG is not a sensitive marker because the portion of urinary MHPG which derives from brain NE is less than was previously assumed.
Several arguments support the view that central MHPG excretion is best represented by the urinary MHPG sulfate fraction. Accordingly, a new strategy has been introduced in last years, involving the separate determination of sulfate and glucuronide conjugates of MHPG as respective markers of central and peripheral NE metabolism. Various biochemical and pharmacological data obtained in healthy subjects and in patients with mental diseases support this hypothesis.
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Baillie T, Boobis AS, Jones DH, Murray S, Reid JL (1977) Studies on the metabolic fate of MHPG in man. Brit J Pharmacol 60: 280
Blombery P, Kopin IJ, Gordon EK, Markey SP, Ebert MH (1979) Metabolism and turnover of MHPG in the monkey. In: Usdin E, Kopin IJ, Barchas J (eds) Catecholamines — basic and clinical frontiers, vol 2. Pergamon Press, pp 1875–1877
Blombery A, Kopin IJ, Gordon EK, Markey SP, Ebert MH (1980) Conversion of MHPG to vanillymandelic acid. Application for the importance of urinary MHPG. Arch Gen Psychiatry 37: 1095–1098
Bond PA (1972) The determination of MHPG in urine and CSF using gas chromatography. Biochem Med 6: 36–45
Bond PA, Dimitrakoudi M, Howlett DR, Jenner FA (1975) Urinary excretion of the sulfate and glucuronide of 3-methoxy-4-hydroxyphenylethyleneglycol in a manic depressive patient. Psychol Med 5: 279–285
Bond PA, Howlett DR, Jenner FA (1979) Urinary excretion of the sulfate and glucuronide of 3-methoxy-4-hydroxyphenylglycol in urine. Biochem Med 10: 219–228
Bond PA, Jenner FA, Sampson G (1972) Daily variations of the urine content of 3-methoxy-4-hydroxyphenylglycol in two manic depressive patients. Psychol Med 12: 81–85
Boobis AR, Murray S, Jones H, Reid JL, Davies JL (1979) Conjugates of 3-methoxy-4-hydroxyphenylglycol in man. In: Usdin E, Kopin IJ, Barchas J (eds) Catecholamines — basic and clinical frontiers, vol 1. Pergamon Press, pp 213–215
Boudet C, Peyrin L, Tavitian E, Claustre J, Favre R (1984) Studies on the central or peripheral origin of free and sulfated 3,4-dihydroxyphenylacetic acid in rat plasma. Eur J Pharmacol 103: 295–301
Buu NT (1985) Relationship between catechol-O-methyltransferase and phenolsulfotransferase in the metabolism of dopamine in the rat brain. J Neurochem 45: 1612–1619
Chase TN, Gordon EK, Ng LKY (1973) Norepinephrine metabolism in the central nervous system of man: studies using 3-methoxy-4-hydroxyphenylglycol levels in cerebrospinal fluid. J Neurochem 21: 581–587
Dekirminjian H, Maas J (1974) 3-methoxy-4-hydroxyphenethyleneglycol in plasma. Clin Chem 52: 203–210
De Met EM, Angelos AE, Gwirtsman HE, Reno RM (1985) Diurnal rythm of MHPG: relationship betweeen plasma and urinary levels. Life Sci 37: 1731–1741
Elsworth JD, Roth RH, Redmond DE (1983) Relative importance of 3-methoxy-4-hydroxyphenylglycol and 3,4-dihydroxyphenylglycol as norepinephrine metabolites in rat, monkey and humans. J Neurochem 41: 786–793
Filser JG, Muller WE, Beckmann H (1986) Should plasma or urinary MHPG be measured in psychiatric research? A critical comment. Br J Psychiatry 148: 95–97
Filser JG, Spira FJ, Gabel A, Beckman H, Muller WE (1988) The evaluation of 4-hydroxy-3-methoxyphenylglycol sulfate as a possible marker of central norepinephrine turnover. Studies in healthy volunteers and depressed patients. J Psychiatr Res 22: 171–182
Filser JG, Spira FJ, Gabel A, Beckmann H, Muller WE (1986) Comparative determination of 3-methoxy-4-hydroxyphenylglycol and its conjugate derivatives in the urine of depressed patients and healthy controls. Pharmacopsychiatry 19: 194–195
Foldes A, Meek JL (1974) Occurence and localization of brain phenolsulfotransferase. J Neurochem 23: 303–307
Gordon EK, Oliver J, Goodwin FK, Chase TN, Post RM (1973) Effect of probenecid on free 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and its sulfate in human cerebrospinal fluid. Neuropharmacology 12: 391–396
Halaris AE, Demet EM, Halari ME (1977) Determination of plasma 3-methoxy-4-hydroxyphenylglycol by pulsed electron capture gas chromatography. Clin Chim Acta 78: 285–294
Hjemdahl P, Sjoquist B, Daleskog M, Eliasson K (1982) A comparison of noradrenaline, MHPG and VMA in plasma as indicators of sympathetic nerve activity in man. Acta Physiol Scand 115: 507–509
Jimerson DC, Ballenger JC, Lake CR, Post RM, Goodwin FK, Kopin IJ (1981) Plasma and CSF MHPG in normals. Psychopharmacol Bull 17: 87–89
Joseph MH, Baker HF, Johnstone EC, Crow TJ (1976) Determination of 3-methoxy-4-hydroxyphenylglycol conjugates in urine. Application to the study of central noradrenaline metabolism in unmedicated chronic schizophrenic patients. Psychopharmacology 51: 47–51
Karege F (1984) Method for total 3-methoxy-4-hydroxyphenylglycol extraction from urine, plasma, and brain tissue using bonded-phase materials: comparison with the ethylacetate extraction method. J Chromatogr 311: 361–388
Karoum F, Lefevre H, Bigelow LB, Costa E (1973) Urinary excretion of 4-hydroxy-3-methoxyphenylglycol and 4-hydroxy-3-methoxyphenylethanol in man and rat. Clin Chim Acta 43: 127
Karoum F, Schwing JM, Potkin SG, Wyatt RJ (1977) Presence of free, sulfate and glucuronide conjugated 3-methoxy-4-hydroxyphenylglycol (MHPG) in human brain, cerebrospinal fluid and plasma. Brain Res 125: 33–339
Kleinmann JE, Bridge P, Karoum F, Speciale S, Staub R, Zalcman S, Gillin JC, Wyatt EJ (1979) Catecholamines and metabolites in the brain of psychotics and normals: post-mortem studies. In: Usdin E, Kopin IJ, Barchas J (eds) Catecholamines — basic and clinical frontiers, vol 2. Pergamon Press, pp 1845–1847
Kohno Y, Tanaka M, Nakagawa R, Toshima N, Nagasaki N (1981) Regional distribution and production rate of 3-methoxy-4-hydroxyphenylglycol (MHPG-SO4) in rat brain. J Neurochem 36: 286–289
Kopin IJ (1985) Catecholamine metabolism: basic aspects and clinical significance. Pharmacol Rev 37: 33–364
Kopin IJ, Jimerson DC, Markey SP, Ebert MH, Polinsky RJ (1984) Disposition and metabolism of MHPG in humans: application to studies in depression. Pharmacopsychiatry 17: 3–8
Kraemer GW, Breese GR, Prange AJ, Moran EC, Lewis JK, Kemnitz JW, Bushnell PJ, Howard JL, Kinney WT (1981) Use of 6-hydroxydopamine to deplete brain catecholamines in the rhesus monkey: effects on urinary catecholamine metabolites and behavior. Psychopharmacology 73: 1–11
Krstulovic AM, Bertani-Dziedzic L, Dziedzic SW, Gitlow SE (1981) Quantitative determination of 3-methoxy-4-hydroxyphenylethyleneglycol and its sulfate conjugate in human lumbar cerebrospinal fluid using liquid chromatography with amperometric detection. J Chromatogr 223: 305–314
Leckmann JF, Maas JW, Heninger GR (1981) Covariance of plasma free 3-methoxy-4-hydroxyphenethyleneglycol and diastolic blood pressure. Eur J Pharmacol 70: 11–120
Maas JW, Davis J, Hanin I, Kocsis JH, Redmond DE, Bowden C, Robins E (1982) Pretreatment neurotransmitter metabolites in response to imipramine and amitryptiline treatment. Psychol Med 12: 37–43
Maas JW, Dekirmenjean H, Garver D, Landis DH (1972) Catecholamine metabolite excretion following intraventricular injection of 6-hydroxy-dopamine. Brain Res 41: 507–511
Maas JW, Hattox SE, Grene NM, Landis DH (1979) 3-methoxy-4-hydroxyphenylethyleneglycol production by human brain in vivo. Science 205: 1025–1027
Maas JW, Hattox SE, Landis DH, Roth RH (1976a) The determination of a brain arterioveinous difference for 3-methoxy-4-hydroxyphenethyleneglycol (MHPG). Brain Res 118: 167–173
Maas JW, Landis DH, Dekirmenjean H (1976b) The occurrence of free vs, conjugated MHPG in non-human and human primate brain. Psychopharmacology 2: 403–410
Maas JW, Leckmann JF (1983) Relationship between CNS noradrenergic function and plasma and urinary MHPG and other norepinephrine metabolites. In: Maas JW (ed) MHPG: Basic mechanisms and psychopathology. Academic Press, New York, pp 33–43
MÄrdh G (1983) Further studies on MHPG oxidation in man. Effect of pool expansion and stereochemistry. J Neurochem 41: 299–301
MÄrdh G, Sjoquist B, Anggard E (1981) Norepinephrine metabolism in man using deuterium labelling: the conversion of 4-hydroxyphenylglycol to 4-hydroxy-3-methoxy mandelic acid. J Neurochem 36: 1181–1185
McGauch JL (1985) Peripheral and central adrenergic influences on brain systems involved in the modulation of memory storage. Ann NY Acad Sci 444: 150–161
Markianos E, Beckmann H (1976) Diurnal changes in dopamine Β-hydroxylase, homovanillic acid and 3-methoxy-4-hydroxyphenylglycol in serum in man. J Neural Transm 39: 79–93
Mulder GJ, Dawson JR, Pang KS (1984) Competition between sulphation and glucuronidation in the rat in vivo: enzyme kinetics and pharmocokinetics of conjugation. Biochem Soc Trans 12: 1719
Murray S, Baillie TA, Davies DS (1977) A non-enzymic procedure for the quantitative analysis of 3-methoxy-4-sulfoxyphenethyleneglycol (MHPG sulfate) in human urine stable isotope dilution and gas chromatography maas spectrometry. J Chromatogr 143: 541–551
O'Keefe Brooksbank BWL (1973) Determination of MHPG, a noradrenaline metabolite, in cerebrospinal fluid and urine. Clin Chem 19: 1031–1035
Peyrin L, Favre R, Broussolle E, Brudon F, Chazot G, Trouillas P (1986) Apport du dosage sélectif du MHPG sulfate urinaire à l'étude du mécanisme de l'action noradrénergique de la métapramine chez le déprimé. Colloque National des Neurosciences, Bordeaux
Peyrin L, Pequignot JM (1983) Free and conjugated 3-methoxy-4-hydroxyphenylglycol in human urine: peripheral origin of glucuronide. Psychopharmacology 79: 16–20
Peyrin L, Pequignot JM, Chauplannaz G, Laurent B, Aimard G (1985) Sulfate and glucuronide conjugates of MHPG in urine of depressed patients: central and peripheral influences. J Neural Transm 63: 255–269
Peyrin L, Pequignot JM, Lacour JR, Fourcade J (1987) Relationships between catecholamine or 3-methoxy-4-hydroxyphenylglycol changes and the mental performance under submaximal exercise in man. Psychopharmacology 93: 188–192
Polinsky RJ, Jimerson DC, Kopin IJ (1984) Chronic autonomic failure: CSF and plasma 3-methoxy-4-hydroxyphenylglycol. Neurology 34: 979–983
Rein G, Glover V, Sandler M (1981) Phenosulfotransferase in human tissue: evidence for multiple forms. In: Usdin E, Sandler M (eds) Phenosulfotransferase in mental health research. Macmillan, New York, pp 98–126
Rein G, Glover V, Sandler M (1982) Multiple forms of PST in human tissues, selective inhibition by dichlore dinitrophenol. Biochem Pharmacol 31: 1893–1898
Rein G, Glover V, Sandler M (1984) Characterization of human brain phenosulfotransferase. J Neurochem 42: 80–85
Reiter C, Mwaluko G, Dunnette J, Van Loon J, Weinshilboum R (1983) Thermolabile and thermostable human platelet phenosulfotransferase-substrate specificity and physical separation. Naunyn Schmiedebergs Arch Pharmacol 324: 140–147
Renskers KJ, Foer KD, Roth JA (1980) Sulfation of dopamine and other biogenic amines by human brain phenolsulfotransferase. J Neurochem 34: 1362–1368
Riederer P, Birkmayer W, Seedmann D, Wuketich ST (1977) Brain noradrenaline and 3-methoxy-4-hydroxyphenylglycol in Parkinson syndrome. J Neural Transm 41: 241–252
Rivett AJ, Francis A, Whittemore R, Roth JA (1984) Sulfate conjugation of dopamine in rat brain: regional distribution of activity and evidence for neuronal localization. J Neurochem 42: 1444–1449
Robinson-White A, Costa JL, Launay JM, Fay DD (1988) Presence of phenolsulfotransferase activity in microvascular enodethelial cells; formation of 5-HT-O-sulfate in intact cells. Microvasc Res 35: 363–367
Shanberg SM, Schildkraut JJ, Breese GR, Kopin IJ (1968) Metabolisms of normetanephrine H3 in rat brain. Identification of conjugated 3-methoxy-4-hydroxyphenylglycol as the major metabolite. Biochem Pharmacol 247–254
Scharpless N, Halbreich U, Feldfogel (1986) Determination of total 3-methoxy-4-hydroxyphenylglycol in plasma using reversed-phase liquid chromatography with electrochemical detection. J Chromatogr 377: 101–109
Sjöquist B, Lindström B, AnggÄrd E (1975) Mass fragmentographic of 4-hydroxy-3-methoxyphenylglycol (MHPG) in urine, cerebrospinal fluid, plasma and tissues using a deuterium-labelled internal standard. J Chromatogr 105: 309–316
Shimizu H, Labrosse H (1969) Metabolism of catecholamines: identification and quantification of 3-methoxy-4-hydroxyphenylglycol glucuronide in human urine. Biochem Pharmacol 18: 1643–1654
Swahn CG, Wiesel FA (1976) Determination of conjugated monoamine metabolites in brain tissue O. J Neural Transm 39: 281–290
Van Kempen GMJ, Wolters WL, Van Elk R (1975) Distribution of 3-methoxy-4-hydroxyphenylethyleneglycol sulfotransferase in brain fractions. J Neurochem 24: 825–827
Wolfson LI, Escriva A (1976) Clearance of 3-methoxy-4-hydroxyphenylglycol from the cerebrospinal fluid. Neurology 26: 781–784
Wong KP (1976) Species differences in the conjugation of 4-hydroxy-3-methoxyphenylethanol with glucuronic acid and sulfuric acid. Biochem J 158: 33–37
Young WF, Okazaki M, Laws ER, Weinshilboum RM (1984) Human brain phenolsulfotransferase: biochemical properties and regional localization. J Neurochem 43: 706–715
Yu PH, Rozdilsky B, Boulton AA (1985) Sulfate conjugation of monoamines in human brain: purification and some properties of an arylamine sulfotransferase from cerebral cortex. J Neurochem 45: 836–843
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Peyrin, L. Urinary MHPG sulfate as a marker of central norepinephrine metabolism: a commentary. J. Neural Transmission 80, 51–65 (1990). https://doi.org/10.1007/BF01245022
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DOI: https://doi.org/10.1007/BF01245022