Advertisement

Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 339, Issue 4, pp 433–440 | Cite as

The release of3H-noradrenaline by p- and m-tyramines and -octopamines, and the effect of deuterium substitution in α-position

  • C. -L. Schönfeld
  • U. Trendelenburg
Article

Summary

The3H-noradrenaline-releasing effects of p- and m-tyramines and -octopamines, either deuterated or not, were studied in isolated vasa deferentia of the rat (COMT inhibited and calcium-free solution in all experiments).

Km, for uptake1 was higher for octopamines than for tyramines, but not increased by the introduction of deuterium in α-position, except for (probably contaminated) deuterated p-octopamine. Other tissues were preloaded with3H-noradrenaline. After inhibition of vesicular uptake and MAO equi-releasing concentrations of the eight amines were strictly correlated withKm, they were 6 to 7 times higher for unsubstituted octopamines than for corresponding tyramines. When only MAO (but not vesicular uptake) was inhibited, this difference decreased to about 4-fold, but the releasing potency of the deuterated amines (relative to their parent amines) remained unchanged (except for p-octopamine). When vesicular uptake and MAO were intact, unsubstituted octopamines were only 1.5 to 2.2 times less potent than the corresponding tyramines. Analysis of the efflux of3H-DOPEG confirmed that this gain in the relative potencies of octopamines is due to their increased ability to mobilize vesicular 3H-noradrenaline; moreover, deuterated amines as well were then better mobilizers than were their parent amines.

It is concluded that, provided vesicular uptake is intact, the introduction of a \-OH-group enhances the ability of indirectly acting sympathomimetic amines to mobilize vesicular noradrenaline; the introduction of deuterium in α-position, on the other hand, enhances this mobilizing effect exclusively when MAO is intact.

Key words

Indirectly acting sympathomimetic amines Tyramine Octopamine Deuterium in α-position Rat vas deferens Noradrenaline outward transport 

Abbreviations used here

COMT

catechol-O-methyl transferase

DOMA

dihydroxymandelic acid

DOPEG

dihydroxyphenylglycol

MAO

monoamine oxidase

OM-fraction

column chromatographic fraction containingall O-methylated metabolites

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Belleau B, Moran J (1963) Deuterium isotope effects in relation to the chemical mechanisms of monoamine oxidase. Ann NY Acad Sci 107:822–839Google Scholar
  2. Belleau B, Burba J, Pindell M, Reiffenstein J (1961) Effect of deuterium substitution in sympathomimetic amines on adrenergic responses. Science 133:102–104Google Scholar
  3. Bönisch H, Trendelenburg U (1987) Veratridine-induced outward transport of3H-noradrenaline from adrenergic nerves of the rat vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 336:621–630Google Scholar
  4. Bönisch H, Trendelenburg U (1988) The mechanism of action of indirectly acting sympathomimetic amines. In: Trendelenburg U, Weiner N (eds) Catecholamines. I. Handbook Exp Pharmacol, vol 90/1. Springer, Berlin Heidelberg New York Tokyo, pp 247–277Google Scholar
  5. Celuch SM, Juorio AV (1987) Effects of deuterium substitution on the chronotropic responses to some sympathomimetic amines in the isolated rat atria. Naunyn-Schmiedeberg's Arch Pharmacol 336:391–395Google Scholar
  6. Dyck LE, Durden DA, Boulton AA (1986) Effects of deuterium substitution on the catabolism of \-phenylethylamine: an in vivo study. J Neurochem 46:399–404Google Scholar
  7. Graefe K-H, Stefano FJE, Langer SZ (1973) Preferential metabolism of3H-(−)-norepinephrine through the deaminated glycol in the rat vas deferens. Biochem Pharmacol 22:1147–1160Google Scholar
  8. Grohmann M, Trendelenburg U (1983) The isotope effect of tritium in 3H-(−)-adrenaline with very high specific activity. NaunynSchmiedeberg's Arch Pharmacol 324:233–234Google Scholar
  9. Grohmann M, Trendelenburg U (1984) The substrate specificity of uptake2 in the rat heart. Naunyn-Schmiedeberg's Arch Pharmacol 328: 164–173Google Scholar
  10. Grohmann M, Henseling M, Cassis L, Trendelenburg U (1986) Errors introduced by a tritium label in position 8 of catecholamines. Naunyn-Schmiedeberg's Arch Pharmacol 332: 34–42Google Scholar
  11. Iversen LL (1967) The uptake and storage of noradrenaline in sympathetic nerves. Cambridge University Press, Cambridge, UKGoogle Scholar
  12. Langeloh A, Trendelenburg U (1987) The mechanism of the3H-noradrenaline releasing effect of various substrates of uptake1 role of monoamine oxidase and of vesicularly stored3H-noradrenaline. Naunyn-Schmiedeberg's Arch Pharmacol 336: 611–620Google Scholar
  13. Langeloh A, Bönisch H, Trendelenburg U (1987) The mechanism of the3H-noradrenaline releasing effect of various substrates of uptake1: multifactorial induction of outward transport. Naunyn-Schmiedeberg's Arch Pharmacol 336:602–610Google Scholar
  14. Michalke W, Langer R, Burger A (1987) Mobilization of biogenic amines from chromaffin-granule ghosts by indirectly acting sympathomimetic amines. Naunyn-Schmiedeberg's Arch Pharmacol 335:R81Google Scholar
  15. Parker EM, Cubeddu LX (1986) Effects of d-amphetamine and dopamine synthesis inhibitors on dopamine and acetylcholine neurotransmission in the striatum. II. Release in the presence of vesicular transmitter stores. J Pharmacol Exp Ther 237:193–203Google Scholar
  16. Parker EM, Cubeddu LX (1988) Comparative effects of amphetamine, phenylethylamine and related drugs on dopamine efflux, dopamine uptake and mazindol binding. J Pharmacol Exp Ther 245:199–210Google Scholar
  17. Schömig E, Trendelenburg U (1987) Simulation of outward transport of neuronal3H-noradrenaline with the help of a two-compartment model. Naunyn-Schmiedeberg's Arch Pharmacol 336:631–640Google Scholar
  18. Snedecor GW, Cochran WG (1980) Statistical methods, 7th edn. Iowa State University Press, USAGoogle Scholar
  19. Stute N, Trendelenburg U (1984) The outward transport of axoplasmic noradrenaline induced by a rise of the sodium concentration in the adrenergic nerve endings of the rat vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 327:124–132Google Scholar
  20. Trendelenburg U, Stefano FJE, Grohmann M (1983) The isotope effect of tritium in3H-noradrenaline. Naunyn-Schmiedeberg's Arch Pharmacol 323:128–140Google Scholar
  21. Yu PH, Barclay S, Davis BA, Boulton AA (1981) Deuterium isotope effects on the enzymatic oxidative deamination of trace amines. Biochem Pharmacol 30:3089–3094Google Scholar
  22. Yu PH, Kazakoff C, Davis BA, Boulton AA (1982) Deuterium isotope effect on the enzymatic oxidation of dopamine and serotonin. Biochem Pharmacol 31:3697–3698Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • C. -L. Schönfeld
    • 1
  • U. Trendelenburg
    • 1
  1. 1.Institut für Pharmakologie und ToxikologieUniversität WürzburgWürzburgGermany

Personalised recommendations