Source and physiological significance of plasma 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol
Abstract
To elucidate the source and physiological significance of plasma 3,4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG) as metabolites of noradrenaline (NA), unlabeled and tritium-labeled NA [( 3H]NA) were infused into conscious rats and the formation of labeled and unlabeled DHPG and MHPG examined. Animals were pretreated with clorgyline to determine the effects of inhibiting monoamine oxidase type A (MAO-A), with desipramine to determine the effects of blockade of NA neuronal uptake, or with reserpine to determine the effects of interference with vesicular translocation of NA. Inhibition of neuronal uptake prevented the formation of DHPG from exogenous NA and halved the formation of MHPG, indicating that DHPG is derived from NA metabolized intraneuronally and that MHPG is derived from NA metabolized extraneuronally and from DHPG produced intraneuronally. Blockade of vesicular translocation of NA with reserpine increased DHPG formation from exogenous NA by 300% and MHPG formation by 70%, consistent with enhanced availability of NA in the neuronal cytoplasm for metabolism by MAO-A. About 74% of NA recaptured by sympathetic nerves was estimated to be sequestered into storage vesicles. Endogenous DHPG and MHPG were derived mainly (60-70%) from leakage of NA from storage vesicles and to a smaller extent (30-40%) from NA recaptured after exocytotic release. An increased plasma DHPG to NA ratio with no change in the MHPG to NA ratio during infusions of physiologically active NA demonstrated that changes in plasma MHPG do not necessarily follow changes in DHPG. Consideration of the intra- and extraneuronal sources of plasma DHPG and MHPG, their main derivation from NA directly released into the neuronal cytoplasm and the influences of neuronal uptake and translocation of NA into storage vesicles is essential for the correct interpretation of plasma concentrations of these metabolites in the evaluation of sympathetic nervous function.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The ratio of plasma NE to DHPG was higher in lean hypertensives than in healthy controls (0.30 vs 0.20, P<0.01).
“The ratio of the plasma concentration of NE to that of its intraneuronal metabolite DHPG, which provides a semiquantitative index of whole body NE neuronal reuptake, 8,15 was higher in lean hypertensives than in healthy controls (0.30 versus 0.20, PϽ0.01, Figure 3).”
From Phenotypic Evidence of Faulty Neuronal Norepinephrine Reuptake in Essential Hypertension (2000) · cites this paper as [15]
Cites
Catecholamines: Basic and Clinical Frontiers
(1979) · Elsevier eBooks · doi:10.1016/c2013-1-15197-0 · Cited by 728 · see citing works
Catecholamine metabolism: basic aspects and clinical significance.
Kopin, I. J. (1985) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06859-0 · Cited by 582 · see citing works
Self-citationEisenhofer, G., Goldstein, D. S., Stull, R., Keiser, H. R., Sunderland, T., Murphy, D. L., & Kopin, I. J. (1986) · Clinical Chemistry · doi:10.1093/clinchem/32.11.2030 · Cited by 477 · see citing works
Self-citationPlasma dihydroxyphenylglycol and the intraneuronal disposition of norepinephrine in humans.
Goldstein, D. S., Eisenhofer, G., Stull, R., Folio, C. J., Keiser, H. R., & Kopin, I. J. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113298 · Cited by 245 · see citing works
Self-citationAssessment of Sympathetic Nervous Function in Humans from Noradrenaline Plasma Kinetics
Esler, M. (1982) · Clinical Science · doi:10.1042/cs0620247 · Cited by 168 · see citing works
Scheinin, M., Chang, W., Jimerson, D. C., et al. (1983) · Analytical Biochemistry · doi:10.1016/0003-2697(83)90442-6 · Cited by 82 · see citing works
Kopin, I. J., Żukowska-Grójec, Z., Bayorh, M. A., & Goldstein, D. S. (1984) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00504372 · Cited by 71 · see citing works
Self-citationThe isotope effect of tritium in3H-noradrenaline
TRENDELENBURG, U., Stefano, F. J. E., & Grohmann, M. J. (1983) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00634260 · Cited by 65 · see citing works
Eisenhofer, G., Ropchak, T. G., Stull, R., Goldstein, D. S., Keiser, H. R., & Kopin, I. J. (1987) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-5347(25)00300-3 · Cited by 40 · see citing works
Self-citationMetabolism of endogenous and exogenous noradrenaline in guinea-pig atria
Starke, K., Hedler, L., & Steppeler, A. (1981) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00503815 · Cited by 35 · see citing works
Izzo, J. L., Thompson, D. A., & Horwitz, D. L. (1985) · Life Sciences · doi:10.1016/0024-3205(85)90593-4 · Cited by 27 · see citing works
Eisenhofer, G., Ropchak, T. G., Kopin, I. J., & Goldstein, D. S. (1988) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)22331-x · Cited by 26 · see citing works
Self-citationSaturation of monoamine oxidase by intraneuronal noradrenaline accumulation
Stefano, F. J. E., & TRENDELENBURG, U. (1984) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00512062 · Cited by 23 · see citing works
Metabolism of endogenous and exogenous noradrenaline in the rabbit perfused heart
Majewski, H., Hedler, L., Steppeler, A., et al. (1982) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00503924 · Cited by 23 · see citing works
The effect of desmethylimipramine on the metabolism of norepinephrine
Zavadil, A. P., Ross, R. J. M., Calil, H. M., Linnoila, M., Blombery, P. A., Jimerson, D. C., Kopin, I. J., & Potter, W. Z. (1984) · Life Sciences · doi:10.1016/0024-3205(84)90070-5 · Cited by 22 · see citing works
Self-citationErrors introduced by a tritium label in position 8 of catecholamines
Grohmann, M. J., Henseling, M., Cassis, L. A., et al. (1986) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00633194 · Cited by 22 · see citing works
Dihydroxyphenylglycol and dihydroxymandelic acid during intravenous infusions of noradrenaline
Eisenhofer, G., Goldstein, D. S., Stull, R., Ropchak, T. G., Keiser, H. R., & Kopin, I. J. (1987) · Clinical Science · doi:10.1042/cs0730123 · Cited by 22 · see citing works
Self-citationPlasma Levels of Catecholamines and Dihydroxyphenylglycol during Antidepressant Drug Treatment
Robinson, D. S., Johnson, G. A., Nies, A., CORCELLA, J., Cooper, T. B., ALBRIGHT, D., & Howard, D. B. (1983) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-198310000-00003 · Cited by 20 · see citing works
Eriksson, B.-M., & Persson, B. (1987) · Journal of Chromatography A · doi:10.1016/s0021-9673(01)94578-9 · Cited by 18 · see citing works
Howes, L. G., MacGilchrist, A., Hawksby, C., Sumner, D. J., & Reid, J. (1986) · Clinical Science · doi:10.1042/cs0710211 · Cited by 14 · see citing works
Alterations in Systemic Haemodynamics Induced by Atriopeptin III
Marks, E. S., Żukowska-Grójec, Z., Ropchak, T. G., et al. (1987) · Journal of Hypertension · doi:10.1097/00004872-198702000-00006 · Cited by 12 · see citing works
Self-citationPlasma noradrenaline and its deaminated metabolites in essential hypertension and pheochromacytoma.
Mizukoshi, M., Hano, T., Kuchii, M., Nishio, I., & Masuyama, Y. (1985) · Japanese Circulation Journal-english Edition · doi:10.1253/jcj.49.1035 · Cited by 10 · see citing works
Studies on the utility of urinary 3,4-dihydroxyphenylethylene-glycol (DHPG) measurement
Li, P. P., Warsh, J. J., Godse, D. D., & Guttman, M. (1985) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/0278-5846(85)90047-8 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Catecholamine Metabolism: A Contemporary View with Implications for Physiology and Medicine
Eisenhofer, G., Kopin, I. J., & Goldstein, D. S. (2004) · Pharmacological Reviews · doi:10.1124/pr.56.3.1 · Cited by 1,072 · see citing works
Self-citationCatecholaminergic systems in stress: structural and molecular genetic approaches
Kvetnansky, R., Sabban, E. L., & Palkovits, M. (2009) · Physiological Reviews · doi:10.1152/physrev.00042.2006 · Cited by 548 · see citing works
Effects of Aging on the Responsiveness of the Human Cardiac Sympathetic Nerves to Stressors
Esler, M. D., Thompson, J. M., Kaye, D. M., Turner, A. G., Jennings, G. L., Cox, H. S., Lambert, G. W., & Seals, D. R. (1995) · Circulation · doi:10.1161/01.cir.91.2.351 · Cited by 183 · see citing works
Eisenhofer, G., Friberg, P., Pacak, K., Goldstein, D. S., Murphy, D. L., Tsigos, C., Quyyumi, A. A., Brunner, H. G., & Lenders, J. W. M. (1995) · Clinical Science · doi:10.1042/cs0880533 · Cited by 123 · see citing works
Self-citationPhenotypic Evidence of Faulty Neuronal Norepinephrine Reuptake in Essential Hypertension
Rumantir, M. S., Kaye, D. M., Jennings, G. L., Vaz, M., Hastings, J. A., & Esler, M. D. (2000) · Hypertension · doi:10.1161/01.hyp.36.5.824 · Cited by 95 · see citing works
Biochemical evidence of sympathetic denervation of the heart in pure autonomic failure
Meredith, I. T., Esler, M. D., Cox, H. S., Lambert, G. W., Jennings, G. L., & Eisenhofer, G. (1991) · Clinical Autonomic Research · doi:10.1007/bf01824986 · Cited by 64 · see citing works
Self-citationMonoaminergic Neuronal Activity in Subcortical Brain Regions in Essential Hypertension
Lambert, G. W., Ferrier, C., Kaye, D. M., Kalff, V., Kelly, M. J., Cox, H. S., Turner, A. G., Jennings, G. L., & Esler, M. D. (1994) · Blood Pressure · doi:10.3109/08037059409101522 · Cited by 32 · see citing works
- Authors
- Eisenhofer, G., Goldstein, D. S., Ropchak, T. G., Nguyen, H. Q., Keiser, H. R., & Kopin, I. J.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Eisenhofer, Graeme
- Venue
- Journal of the Autonomic Nervous System
- Publisher
- Elsevier BV
- Published
- 1988-09
- Volume
- 24
- Issue
- 1-2
- Pages
- 1-14
- ISSN
- 0165-1838 (ISSN-L)
- OpenAlex
- W2004150798
- Cited by
- 98
- References
- 23
- Citations by year
- 2026: 1 · 2024: 2 · 2020: 3 · 2018: 1 · 2016: 1
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the Autonomic Nervous System (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- 3,4-dihydroxyphenylglycol, MHPG, noradrenaline metabolism, monoamine oxidase A, sympathetic nervous function, sympathetic activity, reserpine, clorgyline, desipramine
- MeSH terms
- Animals, Catechols, Clorgyline, Desipramine, Glycols, Male, Methoxyhydroxyphenylglycol, Norepinephrine, Rats, Inbred WKY, Reserpine, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
