Biochemical and Pharmacological Approaches in the Study of Sympathetic Nerves

  • Julius Axelrod


My introduction to biological research was unplanned and accidental. I received a B.S. degree in biology from The City College of New York in 1933 with the hope of studying medicine. At that time, however, it was virtually impossible for a City College graduate to be accepted by a medical school, and I was no exception. Through a friend I heard of an opening for a “volunteer” laboratory assistant in the Department of Bacteriology at New York University. Though this position paid only $25 a month, it gave me an opportunity to work in a research laboratory assisting K. G. Falk in his studies on ester-hydrolyzing enzymes in tumors


Tyrosine Hydroxylase Sympathetic Nerve Pineal Gland Adrenal Medulla Superior Cervical Ganglion 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abel, J.J. (1899): Ueber den blutdruckerregenden Bestandtheil der Nebenniere, das Epinephrin. Hoppe Seylers Z. Physiol. Chem. 28:318–362.CrossRefGoogle Scholar
  2. Aghajanian, G.K., and Bloom, F.E. (1966): Electron microscopic autoradiography of rat hypothalamus after intraventricular H3-norepinephrine. Science 156:402–403.CrossRefGoogle Scholar
  3. Armstrong, M.D., and McMillan, A. (1957): Identification of a major urinary metabolite of norepinephrine. Fed. Proc. 16:146.Google Scholar
  4. Axelrod, J. (1953): Studies on sympathomimetic amines. I. The biotransformation and physiological disposition of 1-ephedrine and 1-norephedrine. J. Pharmacol. Exp. Ther. 109:62–73.PubMedGoogle Scholar
  5. Axelrod, J. (1954): Studies on sympathomimetic amines. II. The biotransformation and physiological disposition of d-amphetamine, d-p-hydroxyamphetamine and d-methamphetamine. J. Pharmacol. Exp. Ther. 110:315–326.PubMedGoogle Scholar
  6. Axelrod, J. (1955a): The enzymatic deamination of amphetamine (Benzedrine). J. Biol. Chem. 214:753–763.PubMedGoogle Scholar
  7. Axelrod, J. (1955b): The enzymatic demethylation of ephedrine. J. Pharmacol. Exp. Ther. 114: 430–438.PubMedGoogle Scholar
  8. Axelrod, J. (1956a): The enzymatic N-demethylation of narcotic drugs. J. Pharmacol. Exp. Ther. 117:322–330.PubMedGoogle Scholar
  9. Axelrod, J. (1956b): Possible mechanism of tolerance to narcotic drugs. Science 124:263–264.PubMedCrossRefGoogle Scholar
  10. Axelrod, J. (1957): O-Methylation of epinephrine and other catechols in vitro and in vivo. Science 126:400–401.PubMedCrossRefGoogle Scholar
  11. Axelrod, J. (1962a): Purification and properties of phenylethanolamine-N-methyl transferase. J. Biol. Chem. 237:1657–1660.PubMedGoogle Scholar
  12. Axelrod, J. (1962b): The enzymatic N-methylation of serotonin and other amines. J. Pharmacol. Exp. Ther. 138:28–33.PubMedGoogle Scholar
  13. Axelrod, J., Brady, R.O., Witkop, B., and Evarts, E.V. (1957): The distribution and metabolism of lysergic acid diethylamide. Ann. NY Acad. Sci. 66:435–444.PubMedCrossRefGoogle Scholar
  14. Axelrod, J., Gordon, E., Hertting, G., Kopin, I.J., and Potter, L.T. (1962): On the mechanism of tachyphylaxis to tyramine in the isolated rat heart. Brit. J. Pharmacol. 19:56–63.PubMedGoogle Scholar
  15. Axelrod, J., Hertting, G., and Potter, L. (1962): Effect of drugs on the uptake and release of H3-norepinephrine in the rat heart. Nature 194:297.PubMedCrossRefGoogle Scholar
  16. Axelrod, J., Schmid, R., and Hammaker, L. (1957): A biochemical lesion in congenital, nonobstructive, non-hemolytic jaundice. Nature 180:1426–1427.PubMedCrossRefGoogle Scholar
  17. Axelrod, J., Senoh, S., and Witkop, B. (1958): O-Methylation of catechol amines in vivo. J. Biol. Chem. 233:697–701.PubMedGoogle Scholar
  18. Axelrod, J., and Tomchick, R. (1958): Enzymatic O-methylation of epinephrine and other catechols. J. Biol. Chem. 233:702–705.PubMedGoogle Scholar
  19. Axelrod, J., Weil-Malherbe, H., and Tomchick, R. (1959): The physiological disposition of H3-epinephrine and its metabolite metanephrine. J. Pharmacol. Exp. Ther. 127:251–256.PubMedGoogle Scholar
  20. Axelrod, J., and Weissbach, H. (1961): Purification and properties of hydroxyindole-O-methyl transferase. J. Biol. Chem. 236:211–213.PubMedGoogle Scholar
  21. Axelrod, J., Whitby, L.G., and Hertting, G. (1961): Effect of psychotropic drugs on the uptake of H3-norepinephrine by tissues. Science 133:383–384.PubMedCrossRefGoogle Scholar
  22. Barger, G., and Dale, H.H. (1910): Chemical structure and sympathomimetic action of amines. J. Physiol. 41:19–59.PubMedGoogle Scholar
  23. Brodie, B.B., and Axelrod, J. (1948a): The estimation of acetanilide and its metabolic products, aniline, N-acetyl p-aminophenol and p-aminophenol (free and total conjugated) in biological fluids and tissues. J. Pharmacol. Exp. Ther. 94:22–28.PubMedGoogle Scholar
  24. Brodie, B.B., and Axelrod, J. (1948b): The fate of acetanilide in man. J. Pharmacol. Exp. Ther. 94:29–38.PubMedGoogle Scholar
  25. Brodie, B.B., and Axelrod, J. (1949): The fate of acetophenetidin (phenacetin) in man and methods for the estimation of acetophenetidin and its metabolites in biological material. J. Pharmacol. Exp. Ther. 97:58–67.PubMedGoogle Scholar
  26. Brodie, B.B., and Axelrod, J. (1950a): The fate of aminopyrine (pyramidon) in man and methods for the estimation of aminopyrine and its metabolites in biological material. J. Pharmacol. Exp. Ther. 99:171–184.PubMedGoogle Scholar
  27. Brodie, B.B., and Axelrod, J. (1950b): The fate of antipyrine in man. J. Pharmacol. Exp. Ther. 98:97–104.PubMedGoogle Scholar
  28. Brown, D.D., Tomchick, R., and Axelrod, J. (1959): The distribution and properties of a histamine-methylating enzyme. J. Biol. Chem. 234:2948–2950.PubMedGoogle Scholar
  29. Brownstein, M., and Axelrod, J. (1974): Pineal gland: 24-hour rhythm in norepinephrine turnover. Science 184:163–165.PubMedCrossRefGoogle Scholar
  30. Brownstein, M., Holz, R., and Axelrod, J. (1973): The regulation of pineal serotonin by a beta adrenergic receptor. J. Pharmacol. Exp. Ther. 186:109–113.PubMedGoogle Scholar
  31. Chen, K.K., and Schmidt, C.F. (1930): Ephedrine and related substances. Medicine (Baltimore) 9:1–117.CrossRefGoogle Scholar
  32. Coupland, R.E. (1965): The Natural History of the Chromaffin Cell. London: Longmans.Google Scholar
  33. Coyle, J.T., and Henry, D. (1973): Catecholamines in fetal and newborn rat brain. J. Neurochem. 21:61–67.PubMedCrossRefGoogle Scholar
  34. Dahlström, A., and Fuxe, K. (1964): Evidence for the existence of monoamine-containing neurons in the central nervous system. Acta Physiol. Scand. (Suppl). 232:1–55.Google Scholar
  35. Deguchi, T., and Axelrod, J. (1973): Supersensitivity and subsensitivity of the β-adrenergic receptor in pineal gland regulated by catecholamine transmitter. Proc. Natl. Acad. Sci. USA 70: 2411–2414.PubMedCrossRefGoogle Scholar
  36. Elliot, T.R. (1904): The action of adrenaline. J. Physiol. 31:xx–xxi.Google Scholar
  37. Euler, U.S. von (1946): A specific sympathomimetic ergone in adrenergic nerve fibers (sympathin) and its relations to adrenaline and nor-adrenaline. Acta Physiol. Scand. 12:73–97.CrossRefGoogle Scholar
  38. Giarman, N.J., and Day, M. (1958): Presence of biogenic amines in the bovine pineal body. Biochem. Pharmacol. 1:235.CrossRefGoogle Scholar
  39. Glowinski, J., and Axelrod, J. (1964): Inhibition of uptake of tritiated noradrenaline in the intact rat brain by imipramine and structurally related compounds. Nature 204:1318–1319.PubMedCrossRefGoogle Scholar
  40. Glowinski, J., and Axelrod, J. (1966): Effects of drugs on the disposition of H3-norepinephrine in the rat brain. Pharmacol. Rev. 18:775–785.PubMedGoogle Scholar
  41. Glowinski, J., Axelrod, J., and Iversen, L.L. (1966): Regional studies of catecholamines in the rat brain. IV. Effects of drugs on the disposition and metabolism of H3-norepinephrine and H3-dopamine. J. Pharmacol. Exp. Ther. 153:30–41.PubMedGoogle Scholar
  42. Greisemer, E.C., Barsky, J., Dragstedt, C.A., Wells, J.A., and Zeller, E.A. (1953): Potentiating effects of iproniazid on the pharmacological action of sympathomimetic amines. Proc. Soc. Exp. Biol. Med. 84:699–701.Google Scholar
  43. Hertting, G., and Axelrod, J. (1961): Fate of tritiated noradrenaline at the sympathetic nerve-endings. Nature 192:172–173.PubMedCrossRefGoogle Scholar
  44. Hertting, G., Potter, L.T., and Axelrod, J. (1962): Effect of decentralization and ganglionic blocking agents on the spontaneous release of H3-norepinephrine. J. Pharmacol. Exp. Ther. 136:289–292.PubMedGoogle Scholar
  45. Hertting, G., Axelrod, J., Kopin, I.J., and Whitby, L.G. (1961): Lack of uptake of catecholamines after chronic denervation of sympathetic nerves. Nature. 189:66.PubMedCrossRefGoogle Scholar
  46. Hoffer, A., Osmond, H., and Smythies, J.R. (1954): Schizophrenia: A new approach. J. Ment. Sci. 100:29–45.PubMedGoogle Scholar
  47. Iversen, L.L., and Glowinski, J. (1966): Regional studies of catecholamines in the rat brain. II. Rate of turnover of catecholamines in various brain regions. J. Neurochem. 13:671–682.PubMedCrossRefGoogle Scholar
  48. Kappers, J.A. (1960): The development, topographic relations and innervation of the epiphysis cerebri in the albino rat. Z. Zellforsch. Mikrosk. Anat. 52:163–215.PubMedCrossRefGoogle Scholar
  49. Langley, J.N. (1901): Observations on the physiological actions of extracts of the supra-renal bodies. J. Physiol. 27:237–256.PubMedGoogle Scholar
  50. Lerner, A.B., Case, J.D., Takahashi, Y., Lee, T.H., and Mori, W. (1958): Isolation of melatonin, the pineal gland factor that lightens melanocytes. J. Am. Chem. Soc. 80:2587.CrossRefGoogle Scholar
  51. Loewi, O. (1921): Über humorale Übertragbarkeit der Herznervenwirkung. Pfluegers Arch. Gesamte Physiol. 189:239–242.CrossRefGoogle Scholar
  52. Molinoff, P.B., Landsberg, L., and Axelrod, J. (1969): An enzymatic assay for octopamine and other β-hydroxylated phenylethylamines. J. Pharmacol. Exp. Ther. 170:253–261.PubMedGoogle Scholar
  53. Mueller, R.A., Thoenen, H., and Axelrod, J. (1969): Increase in tyrosine hydroxylase activity after reserpine administration. J. Pharmacol. Exp. Ther. 169:74–79.PubMedGoogle Scholar
  54. Potter, L.T., and Axelrod, J. (1962): Intracellular localization of catecholamines in tissues of the rat. Nature 194:581–582.PubMedCrossRefGoogle Scholar
  55. Quay, W.B. (1963): Circadian rhythm in rat pineal serotonin and its modifications by estrous cycle and photoperiod. Gen. Comp. Endocrinol. 3:473–479.CrossRefGoogle Scholar
  56. Quinn, G.P., Axelrod, J., and Brodie, B.B. (1958): Species, strain and sex differences in metabolism of hexobarbitone, aminopyrine, antipyrine and aniline. Biochem. Pharmacol. 1:152–159.CrossRefGoogle Scholar
  57. Saavedra, J.M. (1974): Enzymatic isotopic assay for and presence of β-phenylethylamine in brain. J. Neurochem. 22:211–216.PubMedCrossRefGoogle Scholar
  58. Saavedra, J.M., and Axelrod, J. (1972): A specific and sensitive enzymatic assay for tryptamine in tissues. J. Pharmacol. Exp. Ther. 182:363–369.PubMedGoogle Scholar
  59. Saavedra, J.M., and Axelrod, J. (1973): Demonstration and distribution of phenylethanolamine in brain and other tissues. Proc. Natl. Acad. Sci. USA 70:769–772.PubMedCrossRefGoogle Scholar
  60. Saavedra, J.M., Brownstein, M., and Axelrod, J. (1973): A specific and sensitive enzymatic-isotopic microassay for serotonin in tissues. J. Pharmacol. Exp. Ther. 186:508–515.PubMedGoogle Scholar
  61. Schildkraut, J.J. (1965): The catecholamine hypothesis of affective disorders: A review of supporting evidence. Am. J. Psychiat. 122:509–522.PubMedGoogle Scholar
  62. Schmid, R., Hammaker, L., Axelrod, J., and Maxwell, E. (1957): The enzymatic formation of bilirubin glucuronide. Arch. Biochem. Biophys. 70:285–288.PubMedCrossRefGoogle Scholar
  63. Snyder, S.H., Baldessarini, R.J., and Axelrod, J. (1966): A sensitive and specific enzymatic isotopic assay for tissue histamine. J. Pharmacol. Exp. Ther. 153:544–549.PubMedGoogle Scholar
  64. Snyder, S.H., Zweig, M., Axelrod, J., and Fischer, J.E. (1965): Control of the circadian rhythm in serotonin content of the rat pineal gland. Proc. Natl. Acad. Sci. USA 53:301–305.PubMedCrossRefGoogle Scholar
  65. Strominger, J., Kalckar, H., Axelrod, J., and Maxwell, E. (1954): Enzymatic oxidation of uridine diphosphate glucose to uridine diphosphate glucuronic acid. J. Am. Chem. Soc. 76:6411–6412.CrossRefGoogle Scholar
  66. Thoenen, H., and Tranzer, J.P. (1968): Chemical sympathectomy by selective destruction of adrenergic nerve endings with 6-hydroxydopamine. Naunyn-Schmiedebergs Arch. Pharmacol. 261: 271–288.Google Scholar
  67. Weil-Malherbe, H., Axelrod, J., and Tomchick, R. (1959): Blood-brain barrier for adrenaline. Science 129: 1226–1227.PubMedCrossRefGoogle Scholar
  68. Weinshilboum, R., and Axelrod, J. (1971): Serum dopamine-beta-hydroxylase activity. Circ. Res. 28:307–315.PubMedGoogle Scholar
  69. Weinshilboum, R., Thoa, N.B., Johnson, D.G., Kopin, I.J., and Axelrod, J. (1971): Proportional release of norepinephrine and dopamine-β-hydroxylase from sympathetic nerves. Science 174: 1349–1351.PubMedCrossRefGoogle Scholar
  70. Whitby, L.G., Axelrod, J., and Weil-Malherbe, H. (1961): The fate of H3-norepinephrine in animals. J. Pharmacol. Exp. 132:193–201.Google Scholar
  71. Whitby, L.G., Hertting, G., and Axelrod, J. (1960): Effect of cocaine on the disposition of noradrenaline labelled with tritium. Nature 187:604–605.PubMedCrossRefGoogle Scholar
  72. Wolfe, D.E., Potter, L.T., Richardson, K.C., and Axelrod, J. (1962): Localizing tritiated norepinephrine in sympathetic axons by electron microscopic autoradiography. Science 138:440–442.PubMedCrossRefGoogle Scholar
  73. Wurtman, R.J., and Axelrod, J. (1966): Control of enzymatic synthesis of adrenaline in the adrenal medulla by adrenal cortical steroids. J. Biol. Chem. 241:2301–2305.PubMedGoogle Scholar
  74. Wurtman, R.J., Axelrod, J., and Fischer, J.E. (1964): Melatonin synthesis in the pineal gland: Effect of light mediated by the sympathetic nervous system. Science 143:1328–1330.CrossRefGoogle Scholar
  75. Wurtman, R.J., Axelrod, J., and Phillips, L.S. (1963): Melatonin synthesis in the pineal gland: control by light. Science 142:1071–1073.PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Boston 1992

Authors and Affiliations

  • Julius Axelrod

There are no affiliations available

Personalised recommendations