Biosynthesis of indolealkylamines. Physiological release and transport of 5-hydroxytryptamine

  • Paul B. Hagen
  • Leonard H. Cohen
Part of the Handbook of Experimental Pharmacology/Handbuch der experimentellen Pharmakologie book series (HEP, volume 19)


During the past fifty years research on pharmacologically active bases normally present in mammalian tissues has provided considerable insight into the metabolism and physiological functions of acetylcholine, noradrenaline and adrenaline in peripheral nervous tissue and into the role of histamine in hypersensitivity. When, about ten years ago, attention was drawn to the presence in animal tissues of comparable amounts of yet another chemically related base, 5-hydroxytryptamine (Rapport 1948; Rand and Reid 1951; Erspamer and Avsero 1952), which also had pharmacological activity, it was natural that interest should develop in its biosynthesis and metabolism. It is probable that work on the biochemistry of indolealkylamines was considerably stimulated by the expectation that 5-hydroxytryptamine might be particularly important in mental activity and might, in fact, function as a chemical transmitter in the central nervous system much as acetylcholine or noradrenaline were known to function in neuro-muscular and autonomic nervous transmission. This suggestion was based, firstly, on the presence in the central nervous system of trace amounts of 5-hydroxytryptamine (Amin, Crawford and Gaddum 1954) and on the ability of several compounds which are structurally related to 5-hydroxytryptamine, and which block its effect on smooth muscle (Gaddum 1953 b), to influence mental activity (Stoll 1947 ; Gaddum 1953a and 1953b; Woolley and Shaw 1954) and, secondly, on the ability of tranquilizing drugs to reduce the amounts of this newly discovered amine in cerebral tissue (Pletscher, Shore and Brodie 1956). It was thought that knowledge of the biochemistry of 5-hydroxytryptamine might facilitate the development of compounds which could inhibit its synthesis or destruction, or which could mimic or block its pharmacological actions or its physiological activity, whatever that might turn out to be.


Adrenal Medulla Alimentary Canal Decarboxylase Activity Pyridoxal Phosphate Phenylalanine Hydroxylase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adelson, E., J. J. Rheingold and W. H. Crosby: Studies of platelet survival in vivo with P32. J. Lab. clin. Med. 50, 570–576 (1957).PubMedGoogle Scholar
  2. Amin, A. H., T. B. B. Crawford and J. H. Gaddum: The distribution of substrates P and 5-hydroxytryptamine in the central nervous system of the dog. J. Physiol. (Lond.) 126, 596–618 (1954).Google Scholar
  3. Axelrod, J., and H. Weissbach: Purification and properties of hydroxyindole-0-methvl transferase. J. biol. Chem. 236, 211–213 (1961).PubMedGoogle Scholar
  4. Baker, R. V.: Observations on the localization of 5-hydroxytryptamine. J. Physiol. (Lond.) 142, 563–570 (1958).Google Scholar
  5. Baker, R. V.: Mitochondria and storage granules for 5-hydroxytryptamine. J. Physiol. (Lond.) 145, 473–481 (1959).Google Scholar
  6. Baker, R. V., H. Blaschko and G. V. R. Born: The isolation from blood platelets of particles containing 5-hydroxytryptamine and adenosine triphosphate. J. Physiol. (Lond.) 149, 55P–56P (1959).Google Scholar
  7. Baldridge, R. C., L. Borofsky, H. Baird III, F. Reichle and D. Bullock: Relationship of serum phenylalanine levels and ability of phenylketonurics to hydroxylate tryptophan. Proc. Soc. exp. Biol. (N.Y.) 100, 529–531 (1959).Google Scholar
  8. Barer, R., H. Blaschko, G. A. Meek and W. H. Prusoff: Personal communication (1964).Google Scholar
  9. Benditt, E. P., R. L. Wong, M. Arase and E. Roeper: 5-hydroxytryptamine in mast cells. Proc. Soc. exp. Biol. (N.Y.) 90, 303–304 (1955).Google Scholar
  10. Berendes, H., J. A. Anderson, M. A. Ziegler and D. Ruttenberg: Disturbance of tryptophane metabolism in phenylketonuria. Amer. J. Dis. Child. 96, 430 (1958).Google Scholar
  11. Bertaccini, G.: Tissue 5-hydroxytryptamine and urinary ö-hydroxyindoleacetic acid after partial or total removal of the gastro-intestinal tract in the rat. J. Physiol. (Lond.) 153, 239–249 (1960).Google Scholar
  12. Bertaccini, G., and S. Chieppa: Urinary excretion of 5-hydroxyindoleacetic acid after removal of the large intestine in man. Lancet 1960 I, 881CrossRefGoogle Scholar
  13. Bertler, A., A. M. Rosengren and E. Rosengren: In vivo uptake of dopamine and 5-hydr-oxytraptamine by adrenal medullary granules. Experientia (Basel) 16, 418–419 (1960).CrossRefGoogle Scholar
  14. Bertler, A., and E. Rosengren: Distribution of monoamines and enzymes responsible for their formation in brain. Experientia (Basel) 15, 382–384 (1958).CrossRefGoogle Scholar
  15. Birt, A. R., P. Hagen and E. Zebrowski: Amino acid decarboxylase of urticaria pigmentosa mast cells. J. invest. Derm. 37, 273–276 (1961).PubMedGoogle Scholar
  16. Blaschko, H.: The specific action of L-dopa decarboxvlase. J. Physiol. (Lond.) 96, 50P–51P (1939).Google Scholar
  17. Blaschko, H.: The decarboxylation of o-hydroxyphenylalanine. Biochem. J. 44, 268–270 (1949).Google Scholar
  18. Blaschko, H.: Remarks on chemical specificity. Proc. roy. Soc. B 137, 307–311 (1950a).CrossRefGoogle Scholar
  19. Blaschko, H.: Substrate specificity of amino acid decarboxylases. Biochim. biophys. Acta (Amst.) 4, 130–137 (1950b).CrossRefGoogle Scholar
  20. Blaschko, H.: Amine oxidase and amine metabolism. Pharmacol. Rev. 4, 415–458 (1952).PubMedGoogle Scholar
  21. Blaschko, H.: Enzymatic oxidation of 5-hydroxytryptamine in mammalian and cephalopod tissue. Biochem. J. 52, X (1952).PubMedGoogle Scholar
  22. Blaschko, H., G. V. R. Born, A. D’iorio and N. R. Eade: Sedimentation of adrenal medullary granules in hypertonic sucrose. J. Physiol. (Lond.) 132, 44P (1956).Google Scholar
  23. Blaschko, H., J. H. Burn and H. Langemann: The formation of noradrenaline from dihydroxyphenyl-serine. Brit. J. Pharmacol. 5, 431–437 (1950).PubMedGoogle Scholar
  24. Blaschko, H., C. W. Carter, J. R. P. O’brien and G. H. Sloane-Stanley: Pyridoxin in relation to amine formation in the mammalian liver. J. Physiol. (Lond.) 107, 18P–19P (1948).Google Scholar
  25. Blaschko, H., and T. L. Chrusciel: The decarboxylation of amino acids related to tyrosine and their awakening action in reserpine-treated mice. J. Physiol. (Lond.) 151, 272–284 (1960).Google Scholar
  26. Blaschko, H., P. Hagen and A. D. Welch: Observations on the intracellular granules of the adrenal medulla. J. Physiol. (Lond.) 129, 27–49 (1955).Google Scholar
  27. Blaschko, H., and P. Holton: Enzymic formation of ortho-tyramine (o-hvdroxyphenylethylamine). J. Physiol. (Lond.) 110, 482–487 (1950).Google Scholar
  28. Blaschko, H., P. Holton, and G. H. Sloane-Stanley: Enzvmic formation of pressor amines. J. Physiol. (Lond.) 108, 427–439 (1949).Google Scholar
  29. Blaschko, H., and G. H. Sloane-Stanley: Decarboxylation of tyrosine and its derivatives by mammalian and bacterial enzymes. Biochem. J. 42, iii–iv (1948).Google Scholar
  30. Blaschko, H., and A.D. Welch: Localization of adrenaline in cytoplasmic particles of the bovine adrenal medulla. Naunyn-Schmiedeberg’s Arch. exp. Path. Pharmak. 219, 17–22 (1953).CrossRefGoogle Scholar
  31. Born, G. V. R.: Changes in the distribution of phosphorus in platelet rich plasma during clotting. Biochem. J. 68, 695–704 (1958).PubMedGoogle Scholar
  32. Botn, G. V. R., and R.E. Gillson: Studies on the uptake of 5-hydroxytrvptamine by blood platelets. J. Physiol. (Lond.) 146, 472–491 (1959).Google Scholar
  33. Botn, G. V. R., G. I. C. Ingram and R. S. Stacey: The relationship between 5-hydroxytryptamine and adenosine triphosphate in blood platelets. Brit. J. Pharmacol. 13, 62–64 (1958).Google Scholar
  34. Braunstein, A. E.: Pyridoxal phosphate. In: P. D. Boyer, H. Lardy and K. Myrback, The enzymes, vol. 2, part A. New York: Academic Press 1960.Google Scholar
  35. Bülbring, E., and R. C. Y. Lin: The effect of intraluminal application of 5-hydroxytryptamine and 5-hydroxytryptophan on peristalsis: The local production of 5-HT and its release in relation to intraluminal pressure and propulsive activity. J. Physiol. (Lond.) 140, 381–407 (1958).Google Scholar
  36. Burger, M., u. H. Langemann: Bestimmungen von Adrenalin und Noradrenalin sowie von Decarboxylase-und Aminoxydase-Aktivitäten in Zellfraktionen von Phaochromocytomen. Klin. Wschr. 34, 941–944 (1956).PubMedCrossRefGoogle Scholar
  37. Buxton, J., and H. M. Sinclair: Pyridoxal phosphate as a coenzyme of 5-hydroxytryptophan decarboxylase. Biochem. J. 62, 27 P (1956).Google Scholar
  38. Buzard, J. A., and P. D. Nytch: Some characteristics of rat kidney 5-hydroxytryptophan decarboxylase. J. biol. Chem. 227, 225–230 (1957).PubMedGoogle Scholar
  39. Buzard, J. A., and P. D. Nytch: The relation of dietary pyridoxine to the 5-hydroxytryptophan decarboxylase activity of rat kidney. J. biol. Chem. 229, 409–413 (1959).Google Scholar
  40. Carlsson, A., and M. Lindqvist: In vivo decarboxylation of α-methyl DOPA and α-methyl metatyrosine. Acta physiol. scand. 54, 87–94 (1962).PubMedCrossRefGoogle Scholar
  41. Carlsson, A., M. Lindqvist, T. Magnusson and B. Waldeck: On the presence of 3-hydroxvtyramine in brain. Science 127, 471 (1958).PubMedCrossRefGoogle Scholar
  42. Chrusciel, T. L.: Observations on the localization of noradrenaline in homogenates of dog’s hypothalamus. Ciba Foundation Symposium on Adrenergic Mechanisms, p. 539–543. London: Churchill 1960.Google Scholar
  43. Clark, C. T., H. Weissbach and S. Udenfriend: 5-Hydroxytryptophan decarboxylase: preparation and properties. J. biol. Chem. 210, 139–148 (1954).PubMedGoogle Scholar
  44. Cooper, J. R., and I. Melcer: The enzymic oxidation of tryptophan to 5-hydroxytryptophan in the biosynthesis of serotonin. J. Pharmacol. exp. Ther. 132, 265–268 (1961).PubMedGoogle Scholar
  45. Costa, E., and F. Rinaldi: Biochemical and electroencephalographic changes in the brain of rabbits injected with 5-hydroxytryptophan (Influence of chlorpromazine premedication). Amer. J. Physiol. 194, 214–220 (1958).PubMedGoogle Scholar
  46. Dalgliesh, C. E.: Two-dimensional paper chromatography ofin urary indoles and related substances. Biochem. J. 64, 431–485 (1956).Google Scholar
  47. Dalgliesh, C. E., and R. W. Dutton: Biogenesis of 5-hydroxytryptophan. Brit. J. Cancer 11, 296–309 (1957a).PubMedCrossRefGoogle Scholar
  48. Dalgliesh, C. E., and R. W. Dutton: On the site of formation of 5-hydroxytryptophan. Biochem. J. 65, 21P–22P (1957b).Google Scholar
  49. Davidson, J., A. Sjoerdsma, L. N. Loomis and S. Udenfriend: Studies with the serotonin precursor, 5-hydroxytryptophan, in experimental animals and man. J. clin. Invest. 36, 1594–1599 (1957).PubMedCrossRefGoogle Scholar
  50. Davison, A. N., and M. Sandler: Inhibition of 5-hydroxytryptophan decarboxylase by phenylalanine metabolites. Nature (Lond.) 181, 186–187 (1958).CrossRefGoogle Scholar
  51. Dawes, G. S.: Amidines, guanidines and adrenaline inactivation in the liver. Brit. J. Pharmacol. 1, 21–37 (1946).Google Scholar
  52. Demis, D. J., H. Blaschko and A. D. Welch: The conversion of dihydroxy phenylalanine-2-C14 (Dopa) to norepinephrine by bovine adrenal medullary homogenates. J. Pharmacol. exp. Ther. 117, 208–212 (1956).PubMedGoogle Scholar
  53. Demoss, J. A., and D. M. Bonner: Normal and genetically altered tryptophan synthetase from neurospora crassa. Proc. nat. Acad. Sci. (Wash.) 45, 1405–1412 (1959).CrossRefGoogle Scholar
  54. Dengler, H., u. G. Reichel: Hemmung der Dopadecarboxylase durch α-Methyldopa in vivo. Naunyn-Schmiedeberg’s Arch. exp. Path. Pharmak. 234, 275–281 (1958).CrossRefGoogle Scholar
  55. Donaldson jr., R. M., S. J. Gray and V. C. Letsou: 5-hydroxytryptophan as an intermediate of serotonin biosyntheses in malignant carcinoidosis. Lancet 1959 II, 1002–1003.CrossRefGoogle Scholar
  56. Erspamer, V.: Quantitative estimation of 5-hydroxytryptamine in gastrointestinal mucosa, spleen and blood of vertebrates. Ciba Foundation Symposium on Hypertension, p. 78–85. London: Churchill 1954.Google Scholar
  57. Erspamer, V.: Pharmacology of indolealkylamines. Pharmacol. Rev. 6, 425–487 (1954).PubMedGoogle Scholar
  58. Erspamer, V.: Observations on the fate of indolealkylamines in the organism. J. Physiol. (Lond.) 127, 118–133 (1955).Google Scholar
  59. Erspamer, V.: Some observations on the fate of exogenous 5-hydroxytryptamine (enteramine) in the rat. J. Physiol. (Lond.) 133, 1–9 (1956).Google Scholar
  60. Erspamer, V.: Recent research in the field of 5-hydroxytryptamine and related indolealkylamines. Fortschr. Arzneimittelforsch. 3, 151–367 (1961).PubMedGoogle Scholar
  61. Erspamer, V., and B. Asero: Identification of enteramine, the specific hormone of the enterochromaffin cell system, as 5-hydroxytryptamine. Nature (Lond.) 169, 800–801 (1952).CrossRefGoogle Scholar
  62. Erspamer, V., and G. Bertaccini: Observations on the antidiuretic action and the fate of 5-hydroxy-DL-Tryptophan in the rat organism. Arch. int. Pharmacodyn. 137, 6–23 (1962).PubMedGoogle Scholar
  63. Erspamer, V., A. Glässer, B. M. Nobili and C. Pasini: The fate of 4-hydroxytryptophan in the rat organism. Experientia (Basel) 16, 506–507 (1960).CrossRefGoogle Scholar
  64. Erspamer, V., A. Glässer, B. M. Nobili: The fate of 5-hydroxy-N-acetyltryptophan and 5-acetoxy-N-acetyl-tryptophan in the rat organism. Arch. Biochem. 93, 673–674 (1961).PubMedCrossRefGoogle Scholar
  65. Erspamer, V., A. Glässer, C. Pasini and G. Stoppani: In vitro decarboxylation of tryptophans by mammalian decarboxylase. Nature (Lond.) 189, 483 (1961).CrossRefGoogle Scholar
  66. Erspamer, V., and M. B. Nobili: Observations on the fate of oral 4-hvdroxvtryptophan in man. Experientia (Basel) 17, 351–352 (1961).CrossRefGoogle Scholar
  67. Erspamer, V., and M. B. Nobili: Observations on the fate of 4-hydroxy-DL-tryptophan in the Organism of the rat and man. Arch. int. Pharmacodyn. 137, 24–38 (1962).PubMedGoogle Scholar
  68. Erspamer, V., and A. Testini: Observations on the release and turnover rate of 5-hydroxytryptamine in the gastrointestinal tract. J. Pharm. Pharmacol. 11, 618–623 (1959).PubMedCrossRefGoogle Scholar
  69. Ewins, A. J., and P. P. Laidlaw: The syntheses of 3-β-aminoethylindole and its formation from tryptophan. Proc. chem. Soc. 26, 343 (1910).Google Scholar
  70. Fellman, J. H.: Inhibition of DOPA decarboxylase by aromatic acids associated with phenylpyruvic oligophrenia. Proc. Soc. exp. Biol. (N.Y.) 93, 413–414 (1956).Google Scholar
  71. Fellman, J. H.: Purification and properties of adrenal L-dopa decarboxjlase. Enzymologia 20, 366–376 (1959).PubMedGoogle Scholar
  72. Freedland, R. A., M. C. Krakowski and H. A. Waisman: Influence of dietary aromatic amino acids on phenylalanine hydroxylase activity. Fed. Proc. 19, 7 (1960).Google Scholar
  73. Freedland, R. A., I. M. Wadzinski and H.A. Waisman: The enzymatic hydroxylation of tryptophan. Biochem. biophys. Res. Commun. 5, 94–98 (1961).PubMedCrossRefGoogle Scholar
  74. Freter, K., H. Weissbach, S. Udenfriend and B. Witkop: Biochemical and pharmacological studies with D-and L-5-hydroxytryptophan. Proc. Soc. exp. Biol. (N.Y.) 94, 725–728 (1957).Google Scholar
  75. Furth, J., P. Hagen and E. I. Hirsch: Transplantable mastocytoma in the mouse containing histamine, heparin, 5-hydroxvtryptamine. Proc. Soc. exp. Biol. (N.Y.) 95, 824–828 (1957).Google Scholar
  76. Gaddum, J. H.: Antagonism between lysergic acid diethylamide and 5-hydroxvtrvptamine. J. Physiol. (Lond.) 121, 15P (1953a).Google Scholar
  77. Gaddum, J. H.: Drugs antagonistic to 5-hydroxytryptamine. Ciba Foundation on Hypertension 75–77 (1953b).Google Scholar
  78. Gaddum, J. H., and N. J. Giarman: Preliminary studies on the biosynthesis of 5-hvdroxytryptamine. Brit. J. Pharmacol. 11, 88–92 (1956).PubMedGoogle Scholar
  79. Gaddum, J. H., C. O. Hebb, A. Silver and A. A. B. Swan: 5-hydroxytryptamine. Pharmacological action and destruction in perfused lungs. Quart. J. exp. Physiol. 38, 255–262 (1953).PubMedGoogle Scholar
  80. Ganrot, P. O., A. M. Rosengren and E. Rosengren: On the presence of different histidine decarboxylating enzymes in mammalian tissues. Experientia (Basel) 17, 263–264 (1961).CrossRefGoogle Scholar
  81. Giarman, N. J., and L. T. Potter: Release of serotonin by extracts of mammalian tissues. Fed. Proc. 17, 371 (1958).Google Scholar
  82. Gray, E. G., and V. P. Whittaker: The isolation of nerve endings from brain: An electron-microscopic study of cell fragments derived by homogenization and centrifugation. J. Anat. (Lond.) 96, 79–88 (1962).Google Scholar
  83. Green, D. E., L. P. Leloir and V. Nocito: Transaminases. J. biol. Chem. 161, 559–582 (1945).PubMedGoogle Scholar
  84. Hagen, P.: Biosynthesis of norepinephrine from 3,4-dihydroxyphenylethylamine (Dopamine). J. Pharmacol. exp. Ther. 116, 26 (1956).Google Scholar
  85. Hagen, P.: Observations on the substrate specificity of dopa decarboxylase from ox adrenal medulla, human phacochromocytoma and human argent affinoma. Brit. J. Pharmacol. 18, 175–182 (1962).PubMedGoogle Scholar
  86. Hagen, P., and R. J. Barrnett: The storage of amines in the chromaffin cell. Ciba Foundation Symposium on Adrenergic Mechanisms, p. 83–99 (1960).Google Scholar
  87. Hagen, P., R. J. Barrnett, and F. L. Lee: Biochemical and electron microscopic study of particles isolated from mastocytoma cells. J. Pharmacol. exp. Ther. 126, 91–108 (1959).PubMedGoogle Scholar
  88. Hagen, P., and F. L. Lee: Amino acid decarboxylases of mouse mast cells. J. Physiol. (Lond.) 143, 7B–8B (1958).Google Scholar
  89. Hagen, P., N. Weiner, S. Ono and F. L. Lee: Amino acid decarboxylases of mouse mastocytoma tissue. J. Pharmacol. exp. Ther. 130, 9–12 (1960).PubMedGoogle Scholar
  90. Hagen, P., and A. D. Welch: The adrenal medulla and the biosynthesis of pressor amines. Recent Progr. Hormone Res. 12, 27–44 (1956).PubMedGoogle Scholar
  91. Hardisty, R. M., and R. S. Stacey: 5-hydroxytryptamine in normal human platelets. J. Physiol. (Lond.) 130, 711–720 (1955).Google Scholar
  92. Hartmann, W. J., R. I. Akawie and W. G. Clark: Competitive inhibition of 3,4-dihydroxy phenylalanine (Dopa) decarboxylase in vitro. J. biol. Chem. 216, 507–529 (1955).Google Scholar
  93. Hartmann, W. J., R. S. Pogrund, W. Drell and W. G. Clark: Studies on the biosynthesis of arterenol, enzymatic decarboxylation of diastereoisomers of hydroxyphenylserines. J. Amer. chem. Soc. 77, 816–817 (1955).CrossRefGoogle Scholar
  94. Haverback, B. J.: Serotonin and the gastrointestinal tract. Clin. Res. 6, 57 (1958).Google Scholar
  95. Hess, S. M., R. H. Connamacher, M. Ozaki and S. Udenfriend: The effects of α-methyl-dopa and α-methyl-meta-tyrosine on the metabolism of norepinephrine and serotonin in vivo. J. Pharmacol. exp. Ther. 134, 129–138 (1961).PubMedGoogle Scholar
  96. Hess, S. M., B. G. Redfield and S. Udenfriend: The effect of monoamine oxidase inhibitors and tryptophan on the tryptamine content of animal tissues and Urine. J. Pharmacol. exp. Ther. 127, 178–181 (1959a).PubMedGoogle Scholar
  97. Hofmann, A. v.: Die psychotropen Wirkstoffe der mexikanischen Zauberpilze. Separatabdruck aus Chimia 14, 309–318 (1960).Google Scholar
  98. Holtz, P., R. Heise u. K. Lüdtke: Fermentativer Abbau von 1-Dioxyphenylalanin (Dopa) durch Niere. Naunyn-Schmiedeberg’s Arch. exp. Path. Pharmak. 191, 87–118 (1938).CrossRefGoogle Scholar
  99. Holtz, P., and E. Westermann: Dopa (α-(3,4-dihydroxyphenyl)alanine) decarboxylase and histidine decarboxylase in nerve tissue. Naunyn-Schmiedeberg’s Arch. exp. Path. Pharmak. 227, 538–546 (1956).CrossRefGoogle Scholar
  100. Huang, I., S. Tannenbaum and D. Y.-Y. Hsia: Development of 5-hydroxytryptophan decarboxylase activity in rat kidney. Nature (Lond.) 186, 717–718 (1960).CrossRefGoogle Scholar
  101. Humphrey, J. H., and C. C. Toh: Absorption of serotonin (5-hydroxytryptamine) and histamine by dog platelets. J. Physiol. (Lond.) 124, 300–304 (1954).Google Scholar
  102. Ichihara, K., A. Sakamoto, K. Inamori and Y. Sakamoto: Studies on the acid diazo-reaction and 5-or 7-hydroxyindole derivatives. J. Biochem. (Tokyo) 44, 649–659 (1957).Google Scholar
  103. Innes, I. R.: Uptake of 5-hydroxyhyptamine and adrenaline by the liver. Brit. J. Pharmacol. 21, 202–207 (1963).PubMedGoogle Scholar
  104. Jepson, J. B., S. Udenfriend and P. Zaltzman: The enzymic conversion of tryptamine to 6-hydroxytryptamine. Fed. Proc. 18, 254 (1959).Google Scholar
  105. Jepson, J. B., P. Zaltzman and S. Udenfriend: Microsomal hydroxylation of tryptamine, indole-acetic acid and related compounds, to 6-hydroxy derivatives. Biochim. biophys. Acta (Amst.) 62, 91–102 (1962).CrossRefGoogle Scholar
  106. Jervis, G. A.: Phenylpyruvic oligophrenia deficiency of phenylalanine-oxidizing system. Proc. Soc. exp. Biol. (N.Y.) 82, 514–515 (1953).Google Scholar
  107. Kaufman, S.: Studies on the mechanism of the enzymatic conversion of phenylalanine to tyrosine. J. biol. Chem. 234, 2677–2682 (1959).PubMedGoogle Scholar
  108. Kaufman, S., and B. Lovenberg: Further studies on the phenylalanine-hydroxylation cofactor. J. biol. Chem. 234, 2683–2688 (1959).PubMedGoogle Scholar
  109. Kopin, I. J., C. M. B. Pare, J. Axelrod and H. Weissbach: 6-hydroxylation, the major metabolic pathway for melatonin. Biochim. biophys. Acta (Amst.) 40, 377–378 (1960).CrossRefGoogle Scholar
  110. Kuntzman, R., P. A. Shore, D. Bogdanski and B. B. Brodie: Microanalytical procedures for fluorometric assay of brain DOPA-5HTP decarboxylase, norepinephrine and serotonin, and a detailed mapping of decarboxylase activity in brain. J. Neurochem. 6, 226–232 (1961).CrossRefGoogle Scholar
  111. Lagunoff, D., K. B. Lam, E. Roeper and E. P. Benditt: 5-hydroxytryptamine formation from 5-hydroxytryptophan by mast cells. Fed. Proc. 16, 363 (1957).Google Scholar
  112. Langemann, H.: Enzymes and their substrates in the adrenal gland of the ox. Brit. J. Pharmacol. 6, 318–324 (1951).PubMedGoogle Scholar
  113. Langemann, H.: 5-hydroxytryptamine (ed. G. B. Lewis), p. 153–157. London: Pergamon Press 1958.Google Scholar
  114. Langemann, H., u. J. Kägi: Oxytryptamin-und Oxyindolessigsäurebestimmungen bei einem Fall von Carcinoidsyndrom, nebst einigen anderen Untersuchungen über Oxytryptamin. Klin. Wschr. 34, 237–241 (1956).PubMedCrossRefGoogle Scholar
  115. Lerner, A. B., J. D. Case and R. V. Heinzelman: Structure of melatonin. J. Amer. chem. Soc. 81, 6084–6085 (1959).CrossRefGoogle Scholar
  116. Lerner, A. B., J. D. Case, W. Mori and M. R. Wright: Melatonin in peripheral nerve. Nature (Lond.) 183, 1821 (1959).CrossRefGoogle Scholar
  117. Lerner, A. B., J. D. Case, Y. Takahashi, T. H. Lee and W. Mori: Isolation of melatonin, the pineal gland factor that lightens melanocytes. J. Amer. chem. Soc. 80, 2587 (1958).CrossRefGoogle Scholar
  118. Lovenberg, W., H. Weissbach and S. Udenfriend: Aromatic L-amino acid decarboxylase. J. biol. Chem. 237, 89–93 (1962).PubMedGoogle Scholar
  119. Low, F. N., and J. A. Freeman: Electronmicroscopic atlas of normal and leukemic human blood. New York: McGraw-Hill 1958.Google Scholar
  120. Mackay, D., J. F. Riley and D. M. Shepherd: Amino acid decarboxylase activities in rat hepatoma. J. Pharm. Pharmacol. 13, 257–261 (1961).PubMedCrossRefGoogle Scholar
  121. Mandeles, S., R. Koppelman and M. E. Hanke: Deuterium studies on the mechanism of enzymatic amino acid decarboxylation. J. biol. Chem. 209, 327–336 (1954).PubMedGoogle Scholar
  122. Mitoma, C.: Studies on partially purified phenylalanine hydroxylase. Arch. Biochem. 60, 476–484 (1956).PubMedCrossRefGoogle Scholar
  123. Mitoma, C., H. Weissbach and S. Udenfriend: 5-hydroxytryptophan formation and tryptophan metabolism in chromobacterium violaceum. Arch. Biochem. 63, 122–130 (1956).PubMedCrossRefGoogle Scholar
  124. Murphy, G. F., and T. L. Sourkes: Effect of catecholamino acids on the catecholamine content of rat organs. Rev. canad. Biol. 18, 379–388 (1959).PubMedGoogle Scholar
  125. Murphy, G. F., and T. L. Sourkes: The action of antidecarboxylases on the conversion of 3,4-dihydroxyphenylalanine to dopamine in vivo. Arch. Biochem. 93, 338–343 (1961).PubMedCrossRefGoogle Scholar
  126. Oates, J. A., and A. Sjoerdsma: A unique syndrome associated with secretion of 5-hydroxytryptophan by metastatic gastric carcinoids. Amer. J. Med. 32, 333–342 (1962).PubMedCrossRefGoogle Scholar
  127. Odell, T. T., F. N. Gamble and J. Furth: Life span of naturally labelled platelets of rats. Fed. Proc. 12, 398–399 (1953).Google Scholar
  128. Paasonen, M. K., P. D. Maclean and N. J. Giarman: 5-hydroxytryptamine (serotonin, enteramine) content of structures of the limbic system. J. Neurochem. 1, 326–333 (1957).PubMedCrossRefGoogle Scholar
  129. Pare, C. M. B., M. Sandler and R. S. Stacey: 5-hydroxytryptamine deficiency in phenylketonuria. Lancet 1957 I, 551–553.CrossRefGoogle Scholar
  130. Pare, C. M. B., M. Sandler and R. S. Stacey: Decreased 5-hydroxytryptophan decarboxylase activity in phenylketonuria. Lancet 1958 II, 1099–1101.CrossRefGoogle Scholar
  131. Pare, C. M. B., M. Sandler and R. S. Stacey: The relationship between decreased 5-hydroxyindole metabolism and mental defect in phenylketonuria. Arch. Dis. Childh. 34, 422–425 (1959).PubMedCrossRefGoogle Scholar
  132. Parratt, R. J., and G. B. West: 5-hydroxytryptamine and tissue mast cells. J. Physiol. (Lond.) 137, 169–178 (1957).Google Scholar
  133. Pletscher, A., and K. F. Gey: Assay of 5-hydroxytryptophan decarboxylation in intact brain. Nature (Lond.) 190, 918–919 (1961).CrossRefGoogle Scholar
  134. Pletscher, A., P. A. Shore and B. B. Brodie: Serotonin as a mediator of reserpine action in brain. J. Pharmacol. exp. Ther. 116, 84–89 (1956).PubMedGoogle Scholar
  135. Porter, C. C., J. A. Totaro and C. M. Leiby: Some biochemical effects of α-methyl-3,4-di-hydroxyphenylalanine and related compounds in mice. J. Pharmacol. exp. Ther. 134, 139–145 (1961).PubMedGoogle Scholar
  136. Prusoff, W. H.: The distribution of 5-hydroxytryptamine and adenosine triphosphate in cytoplasmic particles of the dog’s small intestine. Brit. J. Pharmacol. 15, 520–524 (1960).PubMedGoogle Scholar
  137. Prusoff, W. H.: Effect of reserpine on the 5-hydroxytryptamine and adenosine triphosphate of the dog intestinal mucosa. Brit. J. Pharmacol. 17, 87–91 (1961).PubMedGoogle Scholar
  138. Rand, M., and G. Reid: Source of “serotonin” in serum. Nature (Lond.) 168, 385 (1951).CrossRefGoogle Scholar
  139. Rapport, M. M.: Serum vasoconstrictor (serotonin) V Presence of creatinine in complex. Proposed structure of vasoconstrictor principle. J. biol. Chem. 180, 961–969 (1948).Google Scholar
  140. Renson, J., F. Goodwin, H. Weissbach and S. Udenfriend: Conversion of tryptophan to 5-hydroxytryptophan by phenylalanine hydroxylase. Biochem. biophys. Res. Commun. 6, 20–25 (1961).PubMedCrossRefGoogle Scholar
  141. Renson, J., H. Weissbach and S. Udenfriend: Hydroxylation of tryptophan by phenylalanine hydroxylase. J. biol. Chem. 237, 2261–2264 (1962).PubMedGoogle Scholar
  142. Rosenberg, J. C., R. B. Davis, W. H. Moran and B. Zimmermann: Serum serotonin concentration and urinary 5-hydroxyindoleacetic acid excretion following intestinal obstruction and resection. Fed. Proc. 18, 503 (1959).Google Scholar
  143. Rosengren, E.: Are dihydroxyphenylalanine decarboxylase and 5-hydroxytryptophan decarboxylase individual enzymes? Acta physiol. scand. 49, 364–369 (1960).PubMedCrossRefGoogle Scholar
  144. Sandler, M., and P. J. D. Snow: An atypical carcinoid tumour secreting 5-hydroxytryptophan. Lancet 1958 I, 137–139.CrossRefGoogle Scholar
  145. Schanberg, S. M., and N. J. Giarman: Uptake of 5-hydroxytryptophan by rat brain. Biochim. biophys. Acta (Amst.) 41, 556–558 (1960).CrossRefGoogle Scholar
  146. Schindler, R.: The conversion of C-labelled tryptophan to 5-hydroxytryptamine by neoplastic mast cells. Biochem. Pharmacol. 1, 323–327 (1958).CrossRefGoogle Scholar
  147. Schindler, R., M. Day and G. A. Fischer: Culture of neoplastic mast cells and their synthesis of 5-hydroxytryptamine and histamine in vitro. Cancer Res. 19, 47–51 (1959).PubMedGoogle Scholar
  148. Schmitz, H., TH. Schleipen u. R. Gross: Freie Nucleotide in normalen menschlichen Blutplättchen. Klin. Wschr. 40, 13–15 (1962).PubMedCrossRefGoogle Scholar
  149. Schott, H. F., and W. G. Clark: Dopa decarboxylase inhibition through the interaction of coenzyme and substrate. J. biol. Chem. 196, 449–462 (1952).PubMedGoogle Scholar
  150. Shore, P.A., A. Pletscher, E. G. Tomich, R. Kuntzman and B. B. Brodie: Release of blood platelet serotonin by reserpine and lack of effect on bleeding time. J. Pharmacol. exp. Ther. 117, 232–236 (1956).PubMedGoogle Scholar
  151. Sjoerdsma, A., J. A. Oates, P. Zaltzman and S. Udenfriend: Identification and assay of urinary tryptamine: Application as an index of MAO inhibition in man. J. Pharmacol. exp. Ther. 126, 217–222 (1959).PubMedGoogle Scholar
  152. Sjoerdsma, A., and S. Udenfriend: Studies on indole metabolism in patients with malignant carcinoid (argentaffinoma). J. clin. Invest. 34, 914–915 (1955).Google Scholar
  153. Sjoerdsma, A., H. Weissbach, L. L. Terry and S. Udenfriend: Further observations on patients with malignant carcinoid. Amer. J. Med. 23, 5–15 (1957).PubMedCrossRefGoogle Scholar
  154. Smith, A. N., L. M. Nyhus, C. E. Dalgliesh, R. W. Dutton, B. Lennox and P. S. Mac-Farlane: Further observations on the endocrine aspects of argentaffinoma. Scot. med. J. 2, 24–38 (1957).PubMedGoogle Scholar
  155. Smith, S. E.: The pharmacological actions of 3,4-dihydroxyphenyl-α-methylalanine (α-methyldopa), an inhibitor of 5-hydroxytryptophan decarboxylase. Brit. J. Pharmacol. 15, 319–327 (1960).PubMedGoogle Scholar
  156. Sourkes, T. L.: Inhibition of dihydroxyphenylalanine decarboxylase by derivatives of phenylalanine. Arch. Biochem. 51, 444–456 (1954).PubMedCrossRefGoogle Scholar
  157. Sourkes, T. L., P. Heneage and Y. Trano: Enzymatic decarboxylation of isomers and derivatives of dihydroxyphenylalanine. Arch. Biochem. 40, 185–193 (1952).PubMedCrossRefGoogle Scholar
  158. Sourkes, T. L., G. F. Murphy, B. Chavez and M. Zielinska: The action of some a-methyl and other amino acids on cerebral catacholamines. J. Neurochem. 8, 109–115 (1961).PubMedCrossRefGoogle Scholar
  159. Stoll, W. A.: Lysergsäure-diäthylamid, ein Phantastikum aus der Mutterkorngruppe. Schweiz. Arch. Neurol. Psychiat. 68, 279–323 (1947).Google Scholar
  160. Sturm, A., u. G. Stüttgen: Nachweis von ö-Hydroxytrjfptamin in menschlichen Mastzellen. Klin. Wschr. 40, 199–201 (1962).PubMedCrossRefGoogle Scholar
  161. Titus, E. O., and S. Udenfriend: Metabolism of 5-hydroxytryptamine (serotonin). Fed. Proc. 13, 411 (1954).Google Scholar
  162. Toh, C. C.: Release of 5-hydroxytryptamine (serotonin) from the dog’s gastro-intestinal tract. J. Physiol. (Lond.) 126, 248–254 (1954).Google Scholar
  163. Toh, C. C.: Release of 5-hydroxytryptamine (serotonin) and histamine from platelets by tissue extracts. J. Physiol. (Lond.) 133, 402–411 (1956).Google Scholar
  164. Udenfriend, S.: Metabolism of 5-hydroxytryptamine. 5-hydroxytryptamine. (Ed. G. P. Lewis). London: Pergamon Press 1958.Google Scholar
  165. Udenfriend, S., D. F. Bogdanski and H. Weissbach: Increase in tissue serotonin by administration of its precursor, 5-hydroxytryptophan. Fed. Proc. 15, 493 (1956).Google Scholar
  166. Udenfriend, S., C. T. Clark, J. Axelrod and B. B. Brodie: Ascorbic acid in aromatic hydroxylation. J. biol. Chem. 208, 731–739 (1954).PubMedGoogle Scholar
  167. Udenfriend, S., C. T. Clark, and E. Titus: The presence of 5-hydroxytryptamine in the venom of Bufo marinus. Experientia (Basel) 8, 379–380 (1952).CrossRefGoogle Scholar
  168. Udenfriend, S., C. T. Clark, and E. Titus: 5-hydroxytryptophan decarboxylase: a new route of metabolism of tryptophan. J. Amer. chem. Soc. 75, 501–502 (1953).CrossRefGoogle Scholar
  169. Udenfriend, S., and J. R. Cooper: The enzymatic conversion of phenylalanine to tyrosine. J. biol. Chem. 194, 503–511 (1952).PubMedGoogle Scholar
  170. Udenfriend, S., C. R. Creveling, H. Posner, B. G. Redfield, J. Daly and B. Witkop: On the inability of tryptamine to serve as a precursor of serotonin. Arch. Biochem. 83, 501–506 (1959).PubMedCrossRefGoogle Scholar
  171. Udenfriend, S., W. M. Lovenberg and H. Weissbach: L-amino acid decarboxylase activity in mammalian tissues and its inhibition by a-methyl DOPA. Fed. Proc. 19, 7 (1960).Google Scholar
  172. Udenfriend, S., E. Titus, H. Weissbach and R. Peterson: Biogenesis and metabolism of 5-hydroxy-indole compounds. J. biol. Chem. 219, 335–344 (1956).PubMedGoogle Scholar
  173. Udenfriend, S., and H. Weissbach: Studies on serotonin (5-hydroxytryptamine) in platelets. Fed. Proc. 13, 412–413 (1954).Google Scholar
  174. Udenfriend, S., and H. Weissbach: Turnover of 5-hydroxytryptamine (serotonin) in tissues. Proc. Soc. exp. Biol. (N.Y.) 97, 748–751 (1958).Google Scholar
  175. Udenfriend, S., H. Weissbach, and D. F. Bogdanski: Increase in tissue serotonin following administration of its precursor 5-hydroxytryptophan. J. biol. Chem. 224, 803–810 (1957).PubMedGoogle Scholar
  176. Udenfriend, S., H. Weissbach, and C. T. Clark: The estimation of 5-hydroxytryptamine (serotonin) in biological tissues. J. biol. Chem. 215, 337–344 (1955).PubMedGoogle Scholar
  177. Waldenström, J., B. Pernow and H. Silwer: Case of metastasizing carcinoma (argentaffinoma?) of unknown origin showing peculiar red flushing and increased amounts of histamine and 5-hydroxytryptamine in blood and urine. Acta med. scand. 156, 73–83 (1956).PubMedCrossRefGoogle Scholar
  178. Weissbach, H., D. F. Bogdanski, B. G. Redfield and S. Udenfriend: Studies on the effect of vitamin B6 on 5-hydroxytryptamine (serotonin) formation. J. biol. Chem. 227, 617–624 (1957).PubMedGoogle Scholar
  179. Weissbach, H., F. Bogdanski and S. Udenfriend: Binding of serotonin and other amines by blood platelets. Arch. Biochem. 73, 492–499 (1958).PubMedCrossRefGoogle Scholar
  180. Weissbach, H., W. Lovenberg and S. Udenfriend: Characteristics of mammalian histidine decarboxylating enzymes. Biochim. Biophys. Acta (Amst.) 50, 177–179 (1961).CrossRefGoogle Scholar
  181. Weissbach, H., B. G. Redfield and J. Axelrod: Biosynthesis of melatonin: Enzymic conversion of serotonin to N-acetylserotonin. Biochim. biophys. Acta (Amst.) 43, 352–353 (1960).CrossRefGoogle Scholar
  182. Weissbach, H., B. G. Redfield and J. Axelrod: The enzymic acetylation of serotonin and other naturally occurring amines. Biochim. biophys. Acta (Amst.) 54, 190–192 (1961).CrossRefGoogle Scholar
  183. Werle, E.: Amino acid decarboxylases and histaminases. Biochem. Z. 311, 270–286 (1942).Google Scholar
  184. Werle, E.: Aminosäure-Decarboxylasen. Angew. Chem. 63, 550–555 (1951).CrossRefGoogle Scholar
  185. Werle, E., and D. Aures: Purification and specificity of 3,4-dihydroxyphenylalanine (dopa) decarboxylase. Hoppe-Seylers Z. physiol. Chem. 316, 45–60 (1959).PubMedCrossRefGoogle Scholar
  186. Werle, E., u. G. Mexxickex: Über die Bildung von Tryptamin aus Tryptophan und von Tyramin aus Tyrosin durch tierisches Gewebe. Biochem. Z. 291, 325–327 (1937).Google Scholar
  187. Westermann, E., H. Balzer u. J. Knell: Hemmung der Serotoninbildung durch α-Methyl-Dopa. Naunyn-Schmiedeberg’s Arch. exp. Path. Pharmak. 234, 194–205 (1958).CrossRefGoogle Scholar
  188. Whittaker, V. P.: A comparison of the distribution of lysosome enzymes and 5-hydroxy-tryptamine with that of acetylcholine in subcellular fractions of Guinea pig brain. Biochem. Pharmacol. 1, 351–352 (1958).CrossRefGoogle Scholar
  189. Wixtrobe, M. M.: Clinical hematology, p. 280. Philadelphia: Lea & Febiger 1961.Google Scholar
  190. Yuwiler, A., E. Geller and S. Eidfson: Studies on 5-hydroxytryptophan decarboxylase. I. In vitro inhibition and substrate interaction. Arch. Biochem. 80, 162–173 (1959).CrossRefGoogle Scholar
  191. Yuwiler, A., E. Geller and S. Eidfson: Studies on 5-hydroxytryptophan decarboxylase. II. Additional inhibition studies and suggestions on the nature of the enzymic site. Arch. Biochem. 89, 143–147 (1960).PubMedCrossRefGoogle Scholar
  192. Yuwiler, A., and R. T. Louttit: Effects of phenvlalanine diet on brain serotonin in the rat. Science 134, 831–832 (1961).PubMedCrossRefGoogle Scholar
  193. Zucker, M. B., and J. Borrelli: Absorption of serotonin (5-hydroxytryptamine) by canine and human platelets. Amer. J. Physiol. 186, 105–110 (1956).PubMedGoogle Scholar

Copyright information

© Springer-Verlag, Berlin · Heidelberg 1966

Authors and Affiliations

  • Paul B. Hagen
  • Leonard H. Cohen

There are no affiliations available

Personalised recommendations