Skip to main content
Log in

Entstehung eines DOPA-pools bei Blockierung der DOPA-Decarboxylase

Formation of a DOPA pool after blockade of the DOPA decarboxylase

  • Published:
Naunyn-Schmiedebergs Archiv für Pharmakologie Aims and scope Submit manuscript

Summary

3H-tyrosine was administered to cats as a continuous i.v. infusion of 30 min duration after inhibition of DOPA-decarboxylase by N-methyl-N′(3-hydroxybenzyl) hydrazine dihydrogen phosphate (= NSD-1034). Subsequently, the content of3H-DOPA in the arterial blood, adrenal glands and adrenal venous blood was measured. For this purpose DOPA was separated from tyrosine and other radioactive tyrosine catabolites by ion exchange chromatography after adsorption onto and elution from alumina.

3H-DOPA was not only detectable in the adrenal glands and in the adrenal venous blood but also in the arterial blood. The content of DOPA in the arterial blood increased linearly during the 30 min infusion period and was 0.5 mμmole/ml at the end of the experiment. This corresponds to a DOPA content in the total blood volume of about 27.5 mμmole/kg body weight. Both adrenals synthesized 0.3 mμmole DOPA per minute and per kg body weight. The significance of the formation of a DOPA pool for the therapeutic use of DOPA decarboxylase inhibitors is discussed.

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

Literatur

  • Altman, P. L., Dittmer, D. S.: Biology Data Book, p. 264. Fed. Am. Soc. Exper. Biol. 1964.

  • Bartholini, G., Blum, J. E., Pletscher, A.: Dopa-induced locomotor Stimulation after inhibition of extracerebral decarboxylase. J. Pharm. Pharmacol.21, 297 (1969).

    Google Scholar 

  • Bertler, A., Carlsson, A., Rosengren, E.: A method for fluorometric determination of adrenaline and noradrenaline in tissues. Acta physiol. scand.44, 273 (1958).

    Google Scholar 

  • Birkofer, L., Hempel, K.: Synthese tritiummarkierter Aminosäuren hoher spezifischer Aktivität. Chem. Ber.96, 1373 (1963).

    Google Scholar 

  • Carlsson, A.: In: H. E. Himwich and W. A. Himwich: Progress in Brain Research, Volume 8; Biogenic Amines, p. 9. Amsterdam-London-New York: Elsevier Publishing Company 1964.

    Google Scholar 

  • Cotzias, G. C., Papavasiliou, P. S., Gellene, R.: Modification of parkinsonism — Chronic treatment withl-dopa. New Engl. J. Med.280, 337 (1969).

    Google Scholar 

  • Crout, J. R.: Catechol amines in urine. Stand. Meth. Clin. Chem.3, 62 (1961).

    Google Scholar 

  • Gjessing, L. R.: Studies of functional neural tumors. I. Urinary 3-methoxy-4-hydroxy-phenyl-metabolites. Scand. J. clin. Lab. Invest.15, 463 (1963a).

    Google Scholar 

  • —: Studies on functional neural tumors. V. Urinary excretion of 3-methoxy-4-hydroxyphenyllactic acid. Scand. J. clin. Lab. Invest.15, 649 (1963b).

    Google Scholar 

  • Hempel, K., Männl, H. F. K.: The conversion of H3-tyrosine to H3-DOPA in the adrenal glands under in vivo conditions. Experientia (Basel)22, 689 (1966).

    Google Scholar 

  • — —: Über die Bildung von H-3-Dopa aus H-3-Tyrosin und die Bestimmung der Dopa-Neubildungsrate in der Nebenniere des Huhnes und der Katze unter in vivo-Bedingungen. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path.257, 391 (1967).

    Google Scholar 

  • — —: Inhibition of tyrosine degradation in vivo by the dopa decarboxylase blocking agent NSD-1034. Experientia (Basel)24, 429 (1968).

    Google Scholar 

  • — —: Quantitative Analyse der Catecholamin-Biosynthese des Nebennierenmarks in vivo und Ruhesekretion neugebildeter Amine unter besonderer Berücksichtigung des Dopamins. Naunyn-Schmiedebergs Arch. Pharmak.264, 363 (1969).

    Google Scholar 

  • Levine, R. J., Sjoerdsma, A.: Dissociation of the decarboxylase-inhibiting and norepinephrine-depleting effects ofα-methyl-dopa,α-ethyl-dopa, 4-bromo-3-hydroxy-benzyloxyamine and related substances. J. Pharmacol. exp. Ther.146, 42 (1964).

    Google Scholar 

  • Nagatsu, T., Levitt, M., Udenfriend, S.: Conversion of L-tyrosine to 3,4-dihydroxyphenylalanine by cell-free preparations of brain and sympathetically innervated tissues. Biochem. biophys. Res. Commun.14, 543 (1964).

    Google Scholar 

  • Rowbottom, J.: The radiolysis of aqueous solutions of tyrosine. J. biol. Chem.212, 877 (1955).

    Google Scholar 

  • Smith, P.: Pathological excretion of 4-hydroxy-3-methoxyphenyllactic acid. Nature (Lond.)205, 1236 (1965).

    Google Scholar 

  • —: Metabolism of dihydroxyphenylalanine in human subjects. Nature (Lond.)213, 802 (1967).

    Google Scholar 

  • Stewart, G. N., Rogoff, J. M.: The spontaneous liberation of epinephrin from the adrenals. J. Pharmacol. exp. Ther.8, 479 (1916).

    Google Scholar 

  • Studnitz, W. von: Methodische und klinische Untersuchungen über die Ausscheidung der 3-Methoxy-4-hydroxymandelsäure. Scand. J. clin. Lab. Invest.12, Suppl. 48 (1960).

    Google Scholar 

  • Udenfriend, S.: Biosynthesis of the sympathetic neurotransmitter, norepinephrine. Harvey Lect.60, 57 (1966).

    Google Scholar 

  • Waalkes, T. P., Udenfriend, S.: A fluorometric method for the estimation of tyrosine in plasma and tissues. J. Lab. clin. Med.50, 733 (1957).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Herrn Prof. Dr. W. Maurer danken wir für die stets großzügige Förderung der Arbeit. Fräulein Regina Kreutz, Frau Susanne Schmidt und Herrn Abdallah Ahmed El Hindy sind wir für interessierte Mitarbeit zu Dank verpflichtet. NSD-1034 wurde freundlicherweise von Smith & Nephew, Research Ltd., Harlow, England, zur Verfügung gestellt. Der Deutschen Forschungsgemeinschaft danken wir für die Gewährung von Sach- und Personalmitteln.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Männl, H.F.K., Lange, H.W. & Hempel, K. Entstehung eines DOPA-pools bei Blockierung der DOPA-Decarboxylase. Naunyn-Schmiedebergs Arch. Pharmak. 266, 50–60 (1970). https://doi.org/10.1007/BF00997782

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00997782

Key-Words

Schlüsselwörter

Navigation