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Metabolic Degradation of Catecholamines. The Relative Importance of Different Pathways under Physiological Conditions and after Administration of Drugs

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Catecholamines

Abstract

The physiological importance of the catecholamines in the peripheral sympathetic nervous system had been well established by 1956 (Von Euler, 1956), and since that time impressive evidence for the importance of these compounds in the central nervous system has accumulated (Glowinski and Baldessarini, 1966). When it was shown that only a small fraction of administered catecholamine is excreted unchanged (Richter, 1940; Von Euler and Luft, 1951; Von Euler et al., 1953), it became important to understand the metabolic transformation and excretion products of these compounds.

This chapter was written by Irwin J. Kopin, M.D. in his private capacity. No official support or endorsement by the U.S. Public Health Service is intended or should be inferred.

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References

  • Armstrong, M.D., Mcmillan, A., Shaw, K.N.F.: 3-Methoxy–4-hydroxy-D-mandelic acid, a urinary metabolite of norepinephrine. Biochim. biophys. Acta (Amst.) 25, 422–423 (1957).

    Article  CAS  Google Scholar 

  • Axelrod, J.: O-Methylation of catechol amines in vitro and in vivo. Science 126, 400–401 (1957).

    Article  PubMed  CAS  Google Scholar 

  • Axelrod, J.: The metabolism of catechol amines in vivo and in vitro. Pharmacol. Rev. 11, (Part 2), 402–408 (1959).

    PubMed  CAS  Google Scholar 

  • Axelrod, J., Albers, R.W., Clemente, C.D.: Distribution of catechol-O-methyl transferase in the nervous system and other tissues. J. Neurochem. 5, 68–72 (1959).

    Article  CAS  Google Scholar 

  • Axelrod, J., Albers, R.W., Clemente, C.D., Laroche, M.J.: Inhibitor of O-methylation of epinephrine and norepinephrine in vitro and in vivo. Science 130, 800 (1959).

    Article  PubMed  CAS  Google Scholar 

  • Axelrod, J., Albers, R.W., Clemente, C.D., Laroche, M.J., Senoh, S., Witkop, B.B.: O-Methylation of catechol amines in vivo. J. biol. Chem. 233, 697–701 (1958).

    PubMed  CAS  Google Scholar 

  • Axelrod, J., Albers, R.W., Clemente, C.D., Laroche, M.J., Senoh, S., Witkop, B.B., Tomchick, R.: Enzymatic O-methylation of norepinephrine and other catechols. J. biol. Chem. 233, 702–705 (1958).

    PubMed  CAS  Google Scholar 

  • Bacq, A.M., Gosseun, L., Dresse, A., Renson, J.: Inhibition of O-methyltransferase by catechol and sensitization to epinephrine. Science 130, 453–454 (1959).

    Article  PubMed  CAS  Google Scholar 

  • Belleau, B., Burba, J.: Tropolones: a unique class of potent noncompetitive inhibitors of S-adenosylmethionine-catechol methyltransferase. Biochim. biophys. Acta (Amst.) 54, 195–196 (1961).

    Article  CAS  Google Scholar 

  • Beyer, K.H., Shapiro, S.H.: Excretion of conjugated epinephrine and related compounds. Amer. J. Physiol. 144, 321–330 (1945).

    CAS  Google Scholar 

  • Blaschko, H., Richter, D., Schlossman, H.J.: Inactivation of adrenaline. J. Physiol. (Lond.) 90, 1–17 (1937).

    CAS  Google Scholar 

  • Brown, G.L., Gillespie, J.S.: Output of sympathetic transmitter from the spleen of the cat. J. Physiol. (Lond.) 138, 81–102 (1957).

    CAS  Google Scholar 

  • Burn, J.H.: Mechanism of action of chemical substances at nerve endings. Acta physiol. scand. 29, 40–49 (1953).

    Article  PubMed  CAS  Google Scholar 

  • Burn, J.H., Philpot, F.J., Trendelenburg, U.: Effect of denervation on enzymes in iris and blood vessels. Brit. J. Pharmacol. 9, 423–429 (1954).

    PubMed  CAS  Google Scholar 

  • Burn, J.H., Philpot, F.J., Trendelenburg, U., Rand, M.J.: The action of sympathomimetic amines in animals treated with reserpine. J. Physiol. (Lond.) 144, 314–346 (1958).

    CAS  Google Scholar 

  • Burn, J.H., Philpot, F.J., Trendelenburg, U., Rand, M.J., Robinson, J.: Effect of denervation on amine oxidase in structures inervated by the sympathetic nerves. Brit. J. Pharmacol. 7, 304–318 (1952).

    PubMed  CAS  Google Scholar 

  • Carlsson, A.: The occurrance, distribution, and physiological role of catecholamines in the nervous system. Pharmacol. Rev. 11, 490–493 (1959).

    PubMed  CAS  Google Scholar 

  • Celander, O., Mellander, S.: Elimination of adrenaline and noradrenaline from circulating blood. Nature (Lond.) 176, 973 (1955).

    Article  CAS  Google Scholar 

  • Corne, S. J., Graham, J.D.P.: Effect of inhibition of monoamine oxidase in vivo on administered adrenaline, noradrenaline, tyramine and serotonin. J. Physiol. (Lond.) 135, 339–349 (1957).

    CAS  Google Scholar 

  • Crout, J.R.: Effect of inhibiting both catechol-O-methyl transferase and monoamine oxidase on cardiovascular responses to norepinephrine. Proc. Soc. exp. Biol. (N.Y.) 108, 482–484 (1961).

    CAS  Google Scholar 

  • Davey, M.J., Farmer, J.B., Reinert, H.: The effects of nialamide on adrenergic function. Brit. J. Pharmacol. 20, 121–134 (1963).

    PubMed  CAS  Google Scholar 

  • Eisenfeld, A. J., Axelrod, J., Krakoff, L.: Inhibition of the extraneuronal accumulation and metabolism of norepinephrine by adrenergic blocking agents. J. Pharmacol, exp. Ther. 156, 107–113 (1966).

    Google Scholar 

  • Eisenfeld, A. J., Axelrod, J., Krakoff, L., Krakoff, L., Iversen, L.L., Axelrod, J.: Inhibition of the extraneuronal metabolism of noradrenaline in the isolated heart by adrenergic blocking agents. Nature (Lond.) 213, 297–298 (1967).

    Article  CAS  Google Scholar 

  • Euler, U.S., Von: Noradrenaline. Springfield, Illinois: Thomas 1956.

    Google Scholar 

  • Euler, U.S., Von, Franksson, E., Hellstrom, J.: Adrenaline and noradrenaline output in urine after unilateral and bilateral adrenalectomy in man. Acta physiol. scand. 31, 1 (1954).

    Google Scholar 

  • Euler, U.S., Von, Franksson, E., Hellstrom, J., Luft, R.: Noradrenaline output in urine after infusion in man. Brit. J. Pharmacol. 6, 286–288 (1951).

    Google Scholar 

  • Euler, U.S., Von, Franksson, E., Hellstrom, J., Luft, R., Sunden, T.: Excretion of urinary adrenaline in normals following intravenous infusion.

    Google Scholar 

  • Euler, U.S., Von, Franksson, E., Hellstrom, J., Luft, R., Sunden, T.: Acta physiol. scand. 30, 249–257 (1953).

    Article  Google Scholar 

  • Evarts, E.V., Gillespie, L., Fleming, T.C., Sjoerdsma, A.: Relative lack of pharmacological action of the 3-methoxy analogue of norepinephrine. Proc. Soc. exp. Biol. (N.Y.) 98, 74–76 (1958).

    CAS  Google Scholar 

  • Fischer, J.E., Kopin, I. J., Axelrod, J.: Evidence for extraneuronal binding of norepinephrine. J. Pharmacol, exp. Ther. 147, 181–185 (1965).

    CAS  Google Scholar 

  • Friend, G., Zileli, M. S., Hamilin, J. R., Reutter, F. W.: Effect of iproniazid on the inactivation of norepinephrine in the human. J. clin. exp. Psychotherap. 19, 61–68 (1958).

    CAS  Google Scholar 

  • Furchgott, R.F., Weinstein, P., Huebl, H., Bozorgmehri, P., Mensendiek, S.R.: Effect of inhibition of monoamine oxidase on response of rabbit aortic strips to sympathomimetic amines. Fed. Proc. 14, 341–342 (1955).

    Google Scholar 

  • Glowinski, J., Axelrod, J.: Effect of drugs on the uptake, release, and metabolism of H3-norepinephrine in the rat brain. J. Pharmacol. 149, 43–49 (1965).

    CAS  Google Scholar 

  • Glowinski, J., Axelrod, J., Baldessarini, R.J.: Metabolism of norepinephrine in the central nervous system. Pharmacol. Rev. 18, 1201–1238 (1966).

    PubMed  CAS  Google Scholar 

  • Griesemer, E.C., Barsky, J., Dragstedt, C.A., Wells, J. A., Zeller, E.A.: Potentiating effect of iproniazid on the pharmacological actions of sympathomimetic amines. Proc. Soc. exp. Biol. (N.Y.) 84, 699–701 (1953).

    CAS  Google Scholar 

  • Hare, M.L.C.: Tyramine oxidase. I. A new enzyme system in liver. Biochem. J. 22, 968–979 (1928).

    PubMed  CAS  Google Scholar 

  • Hertting, G., Axelrod, J.: Fate of tritiated noradrenaline at the sympathetic nerve-endings Nature (Lond.) 192, 172–173 (1961).

    CAS  Google Scholar 

  • Hornykiewicz, O.: Dopamine (3-hydroxy-tyramine) and brain function. Pharmacol. Rev. 18, 925–964 (1966).

    PubMed  CAS  Google Scholar 

  • Iversen, L.L.: The uptake of catecholamines at high perfusion concentrations in the rat isolated heart: a novel catecholamine uptake process. Brit. J. Pharmacol. 25, 18–33 (1965).

    Google Scholar 

  • Iversen, L.L., Glowinski, J., Axelrod, J.: The uptake and storage of H3-norepinephrine in the reserpine-pretreated rat heart. J. Pharmacol, exp. Ther. 150, 173–183 (1965).

    CAS  Google Scholar 

  • Kalsner, S., Nickerson, M.: A method for the study of mechanisms of drug disposition in smooth muscle. Canad. J. Physiol. Pharmacol. 46, 719–730 (1968a).

    Article  CAS  Google Scholar 

  • Kalsner, S., Nickerson, M.:Disposition of norepinephrine and epinephrine in vascular tissue, determined by the technique of oil immersion. J. Pharmacol, exp. Ther. (1969a).

    Google Scholar 

  • Kalsner, S., Nickerson, M.:Effects of reserpine on the disposition of sympathomimetic amines in vascular tissue. Brit. J. Pharmacol. 35, 394–405 (1969b).

    CAS  Google Scholar 

  • Kamijo, K., Koelle, G.B., Wagner, H.H.: Modification of the effects of sympathomimetic amines and of adrenergic nerve stimulation by l-isonicotinyl–2-isopropylhydrazine (IIH) and isonicotinic acid hydrazide (INH). J. Pharmacol, exp. Ther. 117, 213–227 (1955).

    Google Scholar 

  • Koelle, G.B., Det. Valk, A.: Physiological implications of the histochemical localization of monoamine oxidase. J. Physiol. (Lond.) 126, 434–447 (1954).

    CAS  Google Scholar 

  • Kopin, I. J.: Technique for the study of alternative metabolic pathways: epinephrine metabolism in man. Science 131, 1372–1374 (1960).

    Article  PubMed  CAS  Google Scholar 

  • Kopin, I. J., Axelrod, J., Gordon, E.K.: The metabolic fate of H3-epinephrine and C14-metanephrine in the rat. J. biol. Chem. 236, 2109–2113 (1961).

    PubMed  CAS  Google Scholar 

  • Kopin, I. J., Axelrod, J., Gordon, E.K., Gordon, E.K.: Metabolism of norepinephrine-H3 released by tyramine and reserpine. J. Pharmacol. 138, 351–357 (1962).

    CAS  Google Scholar 

  • Kopin, I. J., Axelrod, J., Gordon, E.K., Gordon, E.K.: Metabolism of administered and drug-released norepinephrine–7-H3 in the rat. J. Pharmacol. 140, 207–216 (1963).

    CAS  Google Scholar 

  • Kopin, I. J., Axelrod, J., Gordon, E.K., Gordon, E.K., Horst, W.D.: Studies of uptake of L-norepinephrine-C14. Biochem. Pharmacol. 14, 753–760 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Kopin, I. J., Axelrod, J., Gordon, E.K., Gordon, E.K., Horst, W.D., Hertting, G., Gordon, E.K.: Fate of norepinephrine-H3 in the isolated perfused rat heart. J. Pharmacol, exp. Ther. 138, 34–40 (1962).

    CAS  Google Scholar 

  • Labrosse, E.H., Axelrod, J., Kety, S.S.: O-Methylabion, the principal route of metabolism of epinephrine in man. Science 128, 593–594 (1958).

    Article  PubMed  CAS  Google Scholar 

  • Lightman, S., Iversen, L.L.: The role of Uptake2 in the extraneuronal metabolism of noradrenaline in the isolated rat heart. Brit. J. Pharmacol. 37, 638–649 (1969).

    CAS  Google Scholar 

  • Maclaglan, N.F., Wilkinson, J.H.: Methylation of a phenolic hydroxyl group in the human body. Nature (Lond.) 168, 251 (1951).

    Article  Google Scholar 

  • Maltng, H.M., Highman, B., Spector, S.: Neurologic, neuropathologic and neurochemical effects of prolonged administration of phenylisopropylhydrazine (JB 516) phenylisobutyl-hydrazine (JB 835) and other monoamine oxidase inhibitors. J. Pharmacol, exp. Ther. 137, 334–343 (1962).

    Google Scholar 

  • Nash, C.W., Costa, E., Brodie, B.B.: The actions of reserpine, guanethidine, and metar-aminol on cardiac catecholamine stores. Life Sci. 3, 441–449 (1964).

    Article  PubMed  CAS  Google Scholar 

  • Pletscher, A.: Monoaminoxydase-Hemmer. Dtsch. med. Wschr. 86, 647–657 (1961).

    CAS  Google Scholar 

  • Pfgh, C.E.M., Quastel, J.H.: Oxidation of aliphatic amines by brain and other tissues. Biochem. J. 31, 286–291 (1937).

    Google Scholar 

  • Rabhtjn, J., Feinberg, S. M., Zeller, E. A.: Potentiating effects of iproniazid on the action of some sympathomimetic amines. Proc. Soc. exp. Biol. (N.Y.) 87, 218–220 (1954).

    Google Scholar 

  • Richter, D.: Adrenaline and amine oxidase. Biochem. J. 31, 2022–2028 (1937).

    PubMed  CAS  Google Scholar 

  • Richter, D.: Inactivation of adrenaline in vivo in man. J. Physiol. (Lond.) 98, 361–374 (1940).

    CAS  Google Scholar 

  • Schayer, R.W.: Metabolism of fi-Cu DL-adrenaline. J. biol. Chem. 189, 301–306 (1951).

    PubMed  CAS  Google Scholar 

  • Schayer, R.W., Smiley, R.L., Davis, K. J., Kobayashi, Y.: Role of monoamine oxidase in noradrenaline metabolism. Amer. J. Physiol. 182, 285–286 (1955).

    PubMed  CAS  Google Scholar 

  • Schayer, R.W., Smiley, R.L., Davis, K. J., Kobayashi, Y., Kaplan, E.H.: Metabolism of adrenaline containing isotopic carbon (II). J. biol. Chem. 198, 545–551 (1952).

    PubMed  CAS  Google Scholar 

  • Schayer, R.W., Smiley, R.L., Davis, K. J., Kobayashi, Y., Kaplan, E.H., Kennedy, J.: Metabolism of epinephrine containing isotopic carbon (III). J. biol. Chem. 202, 425–430 (1953).

    PubMed  CAS  Google Scholar 

  • Sharman, D.F., Vanov, S., Vogt, M.: Noradrenaline content in the heart and spleen of the mouse under normal conditions and after administration of some drugs. Brit. J. Pharmacol. 19, 527–533 (1962).

    PubMed  CAS  Google Scholar 

  • Shaw, K.N.F., Mcmillan, A., Armstrong, M.D.: Metabolism of 3, 4-dihydroxyphenyl-alanine. J. biol. Chem. 226, 255–266 (1957).

    CAS  Google Scholar 

  • Shore, P. A., Mead, A.R., Kuntzman, R.G., Spector, S., Brodie, B.B.: Physiological significance of monoamine oxidase in the brain. Science 126, 1063–1064 (1957).

    Article  PubMed  CAS  Google Scholar 

  • Smith, C. B.: The role of monoamine oxidase in the intraneuronal metabolism of norepinephrine released by indirectly-acting sympathomimetic amines or by adrenergic nerve stimulation. J. Pharmacol, exp. Ther. 151, 207–220 (1966).

    CAS  Google Scholar 

  • Snyder, S., Fischer, J., Axelrod, J.: Evidence for the presence of monoamine oxidase in sympathetic nerve endings. Biochem. Pharmacol. 14, 363–365 (1965).

    Article  CAS  Google Scholar 

  • Spector, S., Prockop, D., Shore, P. A., Brodie, B.B.: Effect of iproniazid on brain levels of norepinephrine and serotonin. Science 127, 704 (1958).

    Article  CAS  Google Scholar 

  • Spector, S., Prockop, D., Shore, P. A., Brodie, B.B., Shore, P. A., Brodie, B.B.: Biochemical and pharmacological effects of monoamine oxidase inhibitors, iproniazid, l-phenyl–2-hydrazine propane (JB 516) and l-phenyl–3-hydrazinobutane. J. Pharmacol, exp. Ther. 128, 15–21 (1960).

    CAS  Google Scholar 

  • Stromblad, B.L.R.: Supersensitivity and amine oxidase activity in denervated salivary glands. Acta physiol. scand. 36, 137–153 (1956).

    Article  PubMed  CAS  Google Scholar 

  • Vogt, M.: Concentration of sympathin in different parts of the central nervous system under normal conditions and after administration of drugs. J. Physiol. (Lond.) 123, 451–481 (1954).

    CAS  Google Scholar 

  • Vogt, M.: Catechol amines in brain. Pharmacol. Rev. 11, (Part 2), 483 (1959).

    PubMed  CAS  Google Scholar 

  • Whitby, L.G., Axelrod, J., Weil-Malherbe, H.: The fate of H3-norepinephrine in animals. J. Pharmacol, exp. Ther. 132, 193–201 (1961).

    CAS  Google Scholar 

  • Wurtman, R.J., Kopin, I. J., Horst, D.W., Fischer, J.E.: Epinephrine and organ blood flow: effects of hyperthyroidism, cocaine and sympathetic denervation. Amer. J. Physiol. 207, 1247–1250 (1964).

    PubMed  CAS  Google Scholar 

  • Wylie, D.W., Archer, S., Arnold, A.: Augmentation of pharmacological properties of catecholamines by O-methyl transferase inhibitors. J. Pharmacol, exp. Ther. 130, 239–244 (1960).

    CAS  Google Scholar 

  • Zeller, E.A., Barsky, J.: In vivo inhibition of liver and brain by l-isonicotinyl–2-isopropyl-hydrazine. Proc. Soc. exp. Biol. (N.Y.) 81, 459–461 (1952).

    CAS  Google Scholar 

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  1. Irwin J. Kopin
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  1. University Department of Pharmacology, South Parks Road, Oxford, OX1 3QT, Great Britain

    H. Blaschko

  2. Abt. für Neuropharmakologie, Pharmakologisches Institut der Universität, Obere Zahlbacher Str. 67, D-65, Mainz, Germany

    E. Muscholl

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Kopin, I.J. (1972). Metabolic Degradation of Catecholamines. The Relative Importance of Different Pathways under Physiological Conditions and after Administration of Drugs. In: Blaschko, H., Muscholl, E. (eds) Catecholamines. Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology, vol 33. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-65249-3_8

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  • DOI: https://doi.org/10.1007/978-3-642-65249-3_8

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