Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 323, Issue 4, pp 315–320 | Cite as

The deamination of noradrenaline and 5-hydroxytryptamine by rat brain and heart monoamine oxidase and their inhibition by cimoxatone, toloxatone and MD 770222

  • Margherita Strolin Benedetti
  • Thierry Boucher
  • Christopher J. Fowler
Article

Summary

In both rat brain and heart, noradrenaline and 5-hydroxytryptamine are metabolised predominantly by monoamine oxidase-A. The Km values for 14C-noradrenaline in the rat brain and heart are 290 μM and 300 μM, respectively, whereas for 14C-5-hydroxytryptamine the values are 180 μM and 140 μM, respectively. In the rat brain, mixed substrate experiments suggested that 14C-noradrenaline and 14C-5-hydroxytryptamine are metabolised at the same active centre. Both substrates are inhibited with similar Ki values by the reversible inhibitors cimoxatone, toloxatone and MD 770222.

Key words

Monoamine oxidase Noradrenaline 5-Hydroxytryptamine Rat brain and heart 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Carlsson A, Fowler CJ, Magnusson T, Oreland L, Wiberg A (1981) The activities of monoamine oxidase-A and-B, succinate dehydrogenase and acid phosphatase in the rat brain after hemitransection. Naunyn-Schmiedeberg's Arch Pharmacol 316:51–55Google Scholar
  2. Demarest KT, Smith DJ, Azzaro AJ (1980) The presence of the type A form of monoamine oxidase within nigrostriatal dopaminecontaining neurones. J Pharmacol Exp Ther 215:461–468Google Scholar
  3. Dial EJ, Clarke DE (1979) An explanation for the deamination of phenylethylamine by multiple types of monoamine oxidase. Pharmacol Res Commun 11:491–500Google Scholar
  4. Donnelly CH, Murphy DL (1977) Substrate and inhibitor-related characteristics of human platelet monoamine oxidase. Biochem Pharmacol 26:853–858Google Scholar
  5. Ekstedt B (1979) Substrate specificity of monoamine oxidase in pig liver mitochondria. Med Biol 57:220–223Google Scholar
  6. Filinger EJ, Stefano FJE (1981) MAO-A and MAO-B in the superior cervical ganglion and in the nictitating membrane of the cat. Gen Pharmacol 12:481–484Google Scholar
  7. Fowler CJ (1982) Selective inhibitors of monoamine oxidase types A and B and their clinical usefulness. Drugs Future 7:501–517Google Scholar
  8. Fowler CJ, Callingham BA (1979) The inhibition of rat heart type A monoamine oxidase by clorgyline as a method for the estimation of enzyme active centres. Mol Pharmacol 16:546–555Google Scholar
  9. Fowler CJ, Tipton KF (1982) Deamination of 5-hydroxytryptamine by both forms of monoamine oxidase in the rat brain. J Neurochem 38:733–736Google Scholar
  10. Fowler CJ, Strolin Benedetti M (1983a) The metabolism of dopamine by both forms of monoamine oxidase in the rat brain. J Neurochem (in press)Google Scholar
  11. Fowler CJ, Strolin Benedetti M (1983b) Cimoxatone is a reversible tight-binding inhibitor of the A form of rat brain monoamine oxidase. J Neurochem 40:510–513Google Scholar
  12. Fowler CJ, Callingham BA, Mantle TJ, Tipton KF (1978) Monoamine oxidase A and B: a useful concept? Biochem Pharmacol 27:97–101Google Scholar
  13. Garrick NA, Murphy DL (1981) Differences in the preferential deamination of l-norepinephrine, dopamine and serotonin by MAO in rodent and primate brain. In: Usdin E, Weiner N, Youdim MBH (eds) Function and regulation of monoamine enzymes. Basic and clinical aspects. Mac Millan. London Basingstoke, pp 517–525Google Scholar
  14. Garrick NA, Murphy DL (1982) Monoamine oxidase type A: differences in selectivity towards l-norepinephrine compared to serotonin. Biochem Pharmacol 31:4061–4066Google Scholar
  15. Goridis C., Neff NH (1971) Monoamine oxidase in sympathetic nerves: a transmitter specific enzyme type. Br J Pharmacol 43:814–818Google Scholar
  16. Green AR, Mitchell BD, Tordoff AFC, Youdim MBH (1977) Evidence for dopamine deamination by both type A and type B monoamine oxidase in rat brain in vivo and for the degree of inhibition of enzyme necessary for increased functional activity of dopamine and 5-hydroxytryptamine. Br J Pharmacol 60:343–349Google Scholar
  17. Guffroy C, Fowler CJ, Strolin Benedetti M (1983) The deamination of n-pentylamine by monoamine oxidase and a semicarbazide-sensitive amine oxidase of rat heart. J Pharm Pharmacol (in press)Google Scholar
  18. Hall DWR, Logan BW, Parsons GH (1969) Further studies on the inhibition of monoamine oxidase by M+B9302 (clorgyline). I. Substrate specificity in various mammalian species. Biochem Pharmacol 18:1447–1454Google Scholar
  19. Houslay MD, Tipton KF (1974) A kinetic evaluation of monoamine oxidase activity in rat liver mitochondrial outer membranes. Biochem J 139:645–652Google Scholar
  20. Johnston JP (1968) Some observations upon a new inhibitor of monoamine oxidase in brain tissue. Biochem Pharmacol 17:1285–1297Google Scholar
  21. Kan JP, Strolin Benedetti M (1981) Characteristics of the inhibition of rat brain monoamine oxidase in vitro by MD 780515. J Neurochem 36:1561–1571Google Scholar
  22. Kinemuchi H, Wakin Y, Kamijo K (1980) Substrate selectivity of type A and type B monoamine oxidase in rat brain. J Neurochem 35:109–115Google Scholar
  23. Knoll J, Magyar K (1972) Some puzzling pharmacological effects of monoamine oxidase inhibition. Adv Biochem Psychopharmacol 5:393–408Google Scholar
  24. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
  25. Lyles GA, Callingham BA (1979) Selective influences of age and thyroid hormones on type A monoamine oxidase of the rat heart. J Pharm Pharmacol 31:755–760Google Scholar
  26. Mitra C, Guha SR (1980) Serotonin oxidation by type B MAO of rat brain. Biochem Pharmacol 29:1213–1216Google Scholar
  27. Otsuka S, Kobayashi Y (1964) A radioisotopic assay for monoamine oxidase determinations in human plasma. Biochem Pharmacol 13:995–1006Google Scholar
  28. Parkinson D, Lyles GA, Browne BJ, Callingham BA (1980) Some factors influencing the metabolism of benzylamine by type A and B monoamine oxidase in rat heart and liver. J Pharm Pharmacol 32:844–850Google Scholar
  29. Peers EM, Lyles GA, Callingham BA (1980) The deamination of isoamylamine by monoamine oxidase in mitochondrial preparations from rat liver and heart: a comparison with phenylethylamine. Biochem Pharmacol 29:1097–1102Google Scholar
  30. Strolin Benedetti M, Boucher T, Carlsson A, Fowler CJ (1983) Intestinal metabolism of tyramine by both forms of monoamine oxidase in the rat. Biochem Pharmacol 32:47–52Google Scholar
  31. Student AK, Edwards DJ (1977) Subcellular localisation of type A and type B monoamine oxidase in rat brain. Biochem Pharmacol 26:2337–2342Google Scholar
  32. Suzuki O, Katsumata Y, Oya M (1981) Characterisation of eight biogenic indoleamines as substrates for type A and type B monoamine oxidase. Biochem Pharmacol 30:1553–1558Google Scholar
  33. Tipton KF, Youdim MBH (1976) Assay of monoamine oxidase. In: Wolstenholme GEW, Knight J (eds) Monoamine oxidase and its inhibition. Ciba Foundation Symposium 39. Elsevier, Excerpta Medica, Amsterdam, pp 393–403Google Scholar
  34. Tipton KF, Fowler CJ, Houslay MD (1982) Specificities of the two forms of monoamine oxidase. In: Kamijo K, Usdin E, Nagatsu T (eds) Monoamine oxidase. Basic and clinical frontiers. Elsevier, Excerpta Medica, Amsterdam, pp 87–99Google Scholar
  35. Urwyler S, Von Wartburg JP (1980) Studies on the subcellular localisation of monoamine oxidase types A and B and its importance for the deamination of dopamine in rat brain. Biochem Pharmacol 29:3067–3073Google Scholar
  36. White HL, Tansik RL (1979) Characterisation of multiple substrate binding sites of MAO. In: Singer TP, Von Korff RW, Murphy DL (eds) Monoamine oxidase. Structure, function and altered functions. Academic Press, New York, pp 129–144Google Scholar
  37. Yang HYT, Neff NH (1973) β-Phenethylamine: a specific substrate for type B monoamine oxidase of brain. J Pharmacol Exp Ther 187:365–371Google Scholar
  38. Youdim MBH (1982) Noradrenaline is deaminated by MAO type A and B in vivo. Israel J Med Sci (in press)Google Scholar

Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • Margherita Strolin Benedetti
    • 1
  • Thierry Boucher
    • 1
  • Christopher J. Fowler
    • 1
  1. 1.Centre de Recherche DelalandeRueil-MalmaisonFrance

Personalised recommendations