Advertisement

Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 328, Issue 4, pp 401–406 | Cite as

Influence of MAO A and MAO B on the inactivation of noradrenaline in the saphenous vein of the dog

  • M. M. Caramona
  • D. Araújo
  • F. Brandão
Article

Summary

Specific inhibitors of MAO A (clorgyline 0.1 μmol/l) and of MAO B [(−)deprenyl 10 μmol/l] were used in dog saphenous vein strips in order to study the relative influence of the two types of MAO on: 1. Termination of contractile response to exogenous noradrenaline (NA); 2. Metabolism and accumulation of exogenous (3H)-NA; 3. Metabolism of3H-NA released by electrical stimulation.
  1. 1.

    To study the termination of contractile response to exogenous NA, the oil immersion technique was used to determine the time for half-relaxation. The experiments were performed on strips with or without treatment with cocaine 10 μmol/l (to inhibit neuronal uptake) plus U-0521 100 μmol/l (to inhibit catechol-O-methyl transferase) before and after exposure to MAO inhibitors. Clorgyline, but not (−)deprenyl enhanced significantly the time for half-relaxation of the strips, whether cocaine was present or not.

     
  2. 2.

    To study the metabolism and accumulation of exogenous3H-NA, the strips were incubated (with or without preincubation with cocaine) with3H-NA 0.23 μmol/l and 2.3 μmol/l in the presence and in the absence of MAO inhibitors. The formation of deaminated metabolites was significantly reduced by clorgyline, but not by deprenyl.

     
  3. 3.

    To study the metabolism of3H-NA released by electrical stimulation, the strips were incubated with3H-NA 1.4 μmol/l. In the presence of cocaine and U-0521, field stimulation was applied during two periods of 5 min (10 Hz, 100 V, 2 ms), in the absence or presence of MAO inhibitors. Under these experimental conditions clorgyline, but not deprenyl, abolished DOPEG formation, without affecting the other metabolites.

     

In conclusion, only MAO A seems to be important for the inactivation of noradrenaline.

Key words

Monoamine oxidase A and B Noradrenaline Clorgyline (−)Deprenyl Oxidative deamination Electrical stimulation 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Brandão F (1976) A comparative study of the role played by some inactivation pathways in the disposition of the transmitter in the rabbit aorta and the saphenous vein of the dog. Blood Vessels 13:309–318Google Scholar
  2. Brandão F (1977) Inactivation of norepinephrine in an isolated vein. J Pharmacol Exp Ther 203:23–29Google Scholar
  3. Brandão F, Guimarães S (1972) The termination of action of exogenous noradrenaline in the isolated cat spleen tissue. Naunyn-Schmiedeberg's Arch Pharmacol 275:119–123Google Scholar
  4. Brandão F, Guimarães S (1974) Inactivation of endogenous noradrenaline released by electrical stimulation “in vitro” of dog saphenous vein. Blood Vessels 11:45–54Google Scholar
  5. Brandão F, Paiva MQ, Guimarães S (1980) The role of neuronal and extraneuronal, systems in the metabolism of adrenaline and noradrenaline released from nerve terminals by electrical stimulation. Naunyn-Schmiedeberg's Arch Pharmacol 311:1–7Google Scholar
  6. Caramona MM (1982) Monoamine oxidase of types A and B in the saphenous vein and mesenteric artery of the dog. Naunyn-Schmiedeberg's Arch Pharmacol 319:121–124Google Scholar
  7. Caramona MM (1983) Localization of monoamine oxidase of type A and B in blood vessels with different innervation patterns. Naunyn-Schmiedeberg's Arch Pharmacol 324:185–189Google Scholar
  8. Caramona MM, Osswald W (1985) Effects of clorgyline and (−)deprenyl on the deamination of normetanephrine and noradrenaline in strips and homogenates of the canine saphenous vein. Naunyn-Schmiedeberg's Arch Pharmacol 328:396–400Google Scholar
  9. Farnebo LD, Malmfors T (1971)3H-Noradrenaline released and mechanical response in the field stimulated mouse vas deferens. Acta Physiol Scand (Suppl) 371:1–18Google Scholar
  10. Graefe KH, Stefano F, Langer SZ (1973) Preferential metabolism of3H(−)norepinephrine through the deaminated glycol in the rat vas deferens. Biochem Pharmacol 22:1147–1160Google Scholar
  11. Guimarães S, Osswald W (1969) Adrenergic receptors in, the vein of the dog. Eur J Pharmacol 5:133–140Google Scholar
  12. Kalsner S, Nickerson M (1968) A method for the study of mechanisms of drug disposition in smooth muscle. Can J Physiol Pharmacol 46:719–730Google Scholar
  13. Kalsner S, Nickerson M (1969) Disposition of norepinephrine and epinephrine in vascular tissue, determined by the oil-immersion technique. J Pharmacol Exp Ther 165:152–165Google Scholar
  14. Langer S (1980) Presynaptic regulation of the release of catecholamines. Pharmacol Rev 32:337–362Google Scholar
  15. Luchelli-Fortis MA, Langer SZ (1975) Selective inhibition by hydrocortisone of3H-normetanephrine formation during3H-transmitter release elicited by nerve stimulation in the isolated nerve-muscle preparation of the cat nictitating membrane. Naunyn-Schmiedeberg's Arch Pharmacol 287:261–275Google Scholar
  16. Mack F, Bönisch H (1979) Dissociation contants and lipophilicity of catecholamines and related compounds. Naunyn-Schmiedeberg's Arch Pharmacol 310:1–9Google Scholar
  17. Osswald W, Guimarães S, Coimbra A (1971) The termination of action of catecholamines in the isolated venous tissue of the dog. Naunyn-Schmiedeberg's Arch Pharmacol 269:15–31Google Scholar
  18. Paiva MQ, Guimarães S (1978) A comparative study of the uptake and metabolism of noradrenaline and adrenaline by the isolated saphenous vein of the dog. Naunyn-Schmiedeberg's Arch Pharmacol 303:221–228Google Scholar
  19. Starke K (1981) Presynaptic receptors. Ann Rev Pharmacol Toxicol 21:7–30Google Scholar
  20. Starke K, Steppeler A, Zumstein A, Henseling M, Trendelenburg U (1980) False labelling of commercially available3H-catecholamines? Naunyn-Schmiedeberg's Arch Pharmacol 311: 109–112Google Scholar
  21. Verbeuren TJ, Vanhoutte PM (1982) Deamination of released3H-noradrenaline in the canine saphenous vein. Naunyn-Schmiedeberg's Arch Pharmacol 318:148–157Google Scholar
  22. Wyse DG (1974) On the role of neuronal uptake (uptake1) in the inactivation of noradrenaline by aortic strips. Can J Physiol Pharmacol 52:1102–1109Google Scholar
  23. Wyse DG (1976) Inactivation of neuronal and exogenous norepinephrine in rat tail artery studied by the oil immersion technique. J Pharmacol Exp Ther 198:102–121Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • M. M. Caramona
    • 1
  • D. Araújo
    • 1
  • F. Brandão
    • 1
  1. 1.Laboratório de FarmacologiaFaculdade de MedicinaPortoPortugal

Personalised recommendations