Advertisement

Tetrahydropapaveroline Inhibits Dopamine Uptake in Rat Brain Synaptosomes

  • W. T. Shier
  • J. Rossier
  • L. Y. Koda
  • F. E. Bloom

Abstract

THP, which can be formed by the condensation of dopamine with dopaldehyde, has been proposed to be involved in mediating some of the effects of ethanol on the central nervous system. We have observed that THP induces small granular vesicles (SGVs), visible with the electron microscope, in central dopamine fibers (Koda et al., 1978). In order to investigate the mechanism of SGV induction by THP, we examined dopamine and THP uptake into synaptosomes. [3H]THP (1.25 Ci/mmole), prepared by catalytic exchange labeling, exhibited no active uptake into synaptosomes (kinetics consistent with simple diffusion). THP did exhibit competitive inhibition (Ki=4.2 x 10−5M) of [3H] dopamine uptake (Km=2.6 x 10−7M; Vmax=8.5 nmoles/min/g pellet) in these preparations. It is unlikely that endogenous THP would accumulate to concentrations sufficiently high to inhibit dopamine uptake under physiological conditions.

Keywords

Manganese Dioxide Tritiated Water Dopamine Uptake Trifluoracetic Acid Inhibit Dopamine Uptake 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Cohen, G. and Collins, M. A., 1970, Alkaloids from catecholamines in adrenal tissue: possible role in alcoholism, Science, 167: 1749 1751.Google Scholar
  2. Cohen, G., 1973, A role for tetrahydroisoquinoline alkaloids as false adrenergic neurotransmitters in alcoholism, in: “Alcohol Intoxication and Withdrawal, Experimental Studies,” M. M. Gross, ed., Plenum Press, New York. Adv. Exp. Biol. Med., 35: 33–44.CrossRefGoogle Scholar
  3. Davis, V. E., Brown, H., Huff, J. A. and Cashaw, J. L., 1967, Ethandlinduced alterations of norepinephrine metabolism in man, J. Lab. Clin. Med., 69: 787–799.Google Scholar
  4. Hokfelt, T. and Ljungdahl, A., 1972, Application of cytochemical techniques to the study of suspected transmitter substances in the nervous system, Adv. Biochem. Psychopharmacol., 6: 1–36.Google Scholar
  5. Kirby, G. W., 1967, Biosynthesis of the morphine alkaloids, Science, 155: 170–173.PubMedCrossRefGoogle Scholar
  6. Koda, L. Y., Koob, G. F., Shier, W. T. and Bloom, F. E., 1978a, Tetrahydropapaveroline induces small granular vesicles in brain dopamine fibers, Nature, 276: 281–283.PubMedCrossRefGoogle Scholar
  7. Koda, L. Y., Shier, W. T., Koob, G. F. and Bloom, F. E., 1978b, Electron microscopic localization of tetrahydropapaveroline in the rat caudate nucleus, in: “Catecholamines: Basic and Clinic cal Frontiers,” E. Usdin, J. Kopin and J. Barchas, eds., Pergamon Press, New York.Google Scholar
  8. Pyman, F. L., 1909, CLXXXII Isoquinoline derivatives. Part II. The constitution of the reduction products of papaverine, J. Chem. Soc., 95: 1610–1623.Google Scholar
  9. Snyder, S. H. and Coyle, J. T., 1969, Regional differences in 3Hnorepinephrine and 3H-dopamine uptake into rat brain homogenates, J. Pharmacol. Exp. Ther., 165: 68–86.Google Scholar
  10. Whaley, W. M. and Govindachari, T. R., 1951, The Pictet-Spengler synthesis of tetrahydroisoquinolines and related compounds, Organic Reactions, 6: 151–190.Google Scholar

Copyright information

© Springer Science+Business Media New York 1980

Authors and Affiliations

  • W. T. Shier
    • 1
  • J. Rossier
    • 1
  • L. Y. Koda
    • 1
  • F. E. Bloom
    • 1
  1. 1.Alcohol Research CenterThe Salk InstituteSan DiegoUSA

Personalised recommendations