Skip to main content
Log in

A study of the formation and metabolic disposition of 3,4 dihydroxyphenylethyleneglycol in whole rat brain

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

The catabolism of intraventricularly injected3H-(1)-norepinephrine (NE) by whole rat brain was studied at different time points. Particular attention was given to the formation and metabolic disposition of dihydroxyphenylethyleneglycol (DHPG). Following the intraventricular injection of3H-(1)-NE it was found that 1.0% of the total radioactivity present in whole rat brain was free3H-DHPG, 14.5% was present as conjugated3H-DHPG, and total3H-3-methoxy-4-hydroxyphenylethyleneglycol (3H-MHPG) accounted for 25% of the radioactivity in brain. These data indicate that MHPG and conjugated DHPG are the major products of brain NE and are present in the ratio of 2∶1.3H-DHPG was synthesized, purified, and its identity confirmed. The metabolism of free3H-DHPG in whole rat brain was studied following intraventricular administration. It was found that 30 min after injection 1.5% of the total radioactivity in whole rat brain was present as free3H-DHPG, 34% as conjugated3H-DHPG, 15% as free3H-MHPG, and 31% as conjugated3H-MHPG indicating that free DHPG is rapidly conjugated or converted to MHPG. Finally, in order to determine whether or not peripheral catabolism of intraventricularly administered3H-(1)-NE affects the observed distribution of the3H-metabolic products of norepinephrine present in whole rat brain, rats were pretreated with a MAO inhibitor (2, 9-dimethyl-β-carbolinium iodide [DMCI]) which does not cross the blood brain barrier and then received intraventricular injections of3H-(1)-NE. The amounts of the3H-metabolic products of norepinephrine were then determined. No differences were noted between the DMCI-treated and the control groups. This finding suggests that the observed distribution of the3H-metabolites present in whole rat brain after intraventricular administration of3H-(1)-NE is the products of central catabolism, per se.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

DHPG:

3,4-dihydroxyphenylethyleneglycol

NE:

norepinephrine

MHPG:

3-methoxy-4-hydroxyphenylethyleneglycol

DMCI:

2,9-dimethyl-β-carbolinium iodide

DHMA:

3, 4-dihydroxymandelic acid

References

  • Borison, R., Sabelli, H. C.: Influence of a peripheral monoamine oxidase inhibitor upon the central nervous system levels and pharmacological effects of 2-phenylethylamine. The Pharmacologist17, 258 (1975).

    Google Scholar 

  • Braestrup, C., Nielson, M., Scheel-Kruger, J.: Accumulation and disappearance of noradrenaline and its major metabolites synthesized from intraventricularly injected3H-dopamine in rat brain. J. Neurochem.23, 569–578 (1974).

    PubMed  Google Scholar 

  • Ceasar, P. M., Hague, P., Sharman, D. F., Werdinius, B.: Studies on the metabolism of catecholamines in the central nervous system of the mouse. Br. J. Pharmac.51, 187–195 (1974).

    Google Scholar 

  • de Balbain-Verster, F., Robinson, C. A., Hengeveld, C. A., Bush, E. S.: Freehand cerebroventricular injection technique for unanesthetized rats. Life Sci.10, 1395–1402 (1971).

    Google Scholar 

  • Eccleston, D., Ritchie, I. M.: Sulfate ester formation from catecholamine metabolites and pyrogallol in rat brain in vivo. J. Neurochem.21, 635–646 (1973).

    PubMed  Google Scholar 

  • Glowinski, J., Kopin, I. J., Axelrod, J.: Metabolism of3H-norepinephrine in rat brain. J. Neurochem.12, 25–30 (1965).

    PubMed  Google Scholar 

  • Ho, B. T., Gardner, P. M., Pong, S. F., Walker, K. E.: A new peripheral monoamine oxidase inhibitor: 2, 9-dimethyl-β-carbolinium iodide. Experientia29, 527–529 (1973).

    PubMed  Google Scholar 

  • Maas, J. W., Landis, D. H.: In vivo studies of the metabolism of norepinephrine in the central nervous system. J. Pharmac. Exp. Ther.163, 147–162 (1968).

    Google Scholar 

  • Mannarino, E., Kirshner, N., Nasbold, B. S.: The Metabolism of14C-noradrenaline by cat brain in vivo. J. Neurochem.10, 373–379 (1963).

    Google Scholar 

  • Meek, J. L., Neff, N. H.: Biogenic amines and their metabolites as substrates for phenol sulfotransferase of brain and liver. J. Neurochem.21, 1–9 (1973).

    PubMed  Google Scholar 

  • Merits, J.: The effect of changes in the calcium content of the cerebrospinal fluid upon spinal reflex activity in the dog. Am. J. Physiol.131, 67–72 (1940).

    Google Scholar 

  • Rutledge, C. O., Jonason, J.: Metabolic pathways of dopamine and norepinephrine in rabbit brain in vitro. J. Pharmac. Exp. Ther.153, 493 to 502 (1967).

    Google Scholar 

  • Schanberg, S. M., Breese, G. R., Schildkraut, J. J., Gordon, E. K., Kopin, I. J.: 3-Methoxy-4-hydroxyphenylglycol sulfate in brain and cerebrospinal fluid. Biochem. Pharmac.17, 2006–2008 (1968 b).

    Google Scholar 

  • Schanberg, S. M., Schildkraut, J. J., Breese, G. R., Kopin, I. J.: Metabolism of normetanephrine-3H in rat brain-identification of conjugated 3-methoxy-4-hydroxyphenylglycol as the major metabolite. Biochem. Pharmac.17, 247–254 (1968 a).

    Google Scholar 

  • Schweitzer, J. W., Friedhoff, A. J.: A new method for the determination of labelled dopamine, norepinephrine and their metabolites in rat brain homogenate. Life Sci.8, 173–182 (1969).

    PubMed  Google Scholar 

  • Sharman, D. F.: Glycol metabolites of noradrenaline in brain tissue. Br. J. Pharmac.36, 523–534 (1969).

    Google Scholar 

  • Sugden, R. F., Eccleston, D.: Glycol sulfate ester formation from [14C] noradrenaline in brain and the influence of a COMT inhibitor. J. Neurochem.18, 2461–2468 (1971).

    PubMed  Google Scholar 

  • Stone, E. A.: Accumulation and metabolism of norepinephrine in rat hypothalamus after exhaustive stress. J. Neurochem.21, 589–601 (1973).

    PubMed  Google Scholar 

  • Taylor, R. M., Laverty, R.: The metabolism of tritiated dopamine in regions of the rat brain in vivo-II. J. Neurochem.16, 1367–1376 (1969).

    PubMed  Google Scholar 

  • Weil-Malherbe, H.: The estimation of 3, 4-dihydroxymandelic acid in urine and its excretion by man. J. Lab. Clin. Med.69, 1025–1035 (1967).

    PubMed  Google Scholar 

  • Weil-Malherbe, H., Bone, A. D.: The chemical estimation of adrenaline-like substances in blood. Biochem. J.51, 311–318 (1952).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported in part by NIMH Grant MH 24393.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gale, S.W., Maas, J.W. A study of the formation and metabolic disposition of 3,4 dihydroxyphenylethyleneglycol in whole rat brain. J. Neural Transmission 41, 59–72 (1977). https://doi.org/10.1007/BF01252965

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01252965

Keywords

Navigation