Advertisement

Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 324, Issue 3, pp 190–195 | Cite as

Monoamine oxidase in pancreatic islets, exocrine pancreas, and liver from rats. Characterization with clorgyline, deprenyl, pargyline, tranylcypromine, and amezinium

  • S. Lenzen
  • H. Nahrstedt
  • U. Panten
Article

Summary

Monoamine oxidase (MAO) was characterized in tissue homogenates from pancreatic islets, exocrine pancreas, and liver from rats. Phenylethylamine was preferentially deaminated by pancreatic islet MAO while 5-hydroxytryptamine was preferentially deaminated by MAO from exocrine pancreas, and tyramine was a good substrate for both tissues. All three substrates were well deaminated by liver tissue. Clorgyline, a selective inhibitor of MAO-A, preferentially inhibited deamination of 5-hydroxytryptamine by all three tissue homogenates, while deprenyl, a selective inhibitor of MAO-B, preferentially inhibited deamination of phenylethylamine. In the case of pargyline, a less selective MAO-B inhibitor, the preference in favour of phenylethylamine was less pronounced. According to these results, MAO in pancreatic islets can be classified as predominantly type B enzyme species and MAO in exocrine pancreas as predominantly type A enzyme species while both types of the enzyme are present in the liver. Using the same three MAO substrates and compared with the effects of the selective enzyme inhibitors, clorgyline and deprenyl, tranylcypromine can be classified as a potent nonselective inhibitor of MAO in homogenates of all three tissues investigated with a slight preference in favour of the inhibition of the B-form of the enzyme, while in contrast amezinium can be classified as a weak nonselective inhibitor of MAO with a slight preference in favour of the inhibition of the A-form of the enzyme. All MAO inhibitors tested also inhibited insulin secretion by isolated incubated rat pancreatic islets, however only at IC50 which were two to three decimal powers higher than those necessary for the inhibition of the MAO activity, thus indicating that inhibition of MAO activity and inhibition of insulin secretion are apparently not closely related.

Key words

Monoamine oxidase Pancreatic islets Exocrine pancreas Liver Amezinium 

Abbreviation used

MAO

monoamine oxidase

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aleyassine H, Gardiner RJ (1975) Dual action of antidepressant drugs (MAO inhibitors) on insulin release. Endocrinology 96:702–710Google Scholar
  2. Dean PM (1973) Ultrastructural morphometry of the pancreatic β-cell. Diabetologia 9:115–119Google Scholar
  3. Ekstedt B (1976) Substrate specificity of the different forms of monoamine oxidase in rat liver mitochondria. Biochem Pharmacol 25:1133–1138Google Scholar
  4. Feldman JM, Chapman B (1975a) Characterization of pancreatic islet monoamine oxidase. Metabolism 24:581–588Google Scholar
  5. Feldman JM, Chapman B (1975b) Monoamine oxidase inhibitors: nature of their interaction with rabbit pancreatic islets to alter insulin secretion. Diabetologia 11:487–494Google Scholar
  6. Fowler CJ, Callingham BA (1978) Substrate-selective activation of rat liver mitochondrial monoamine oxidase by oxygen. Biochem Pharmacol 27:1995–2000Google Scholar
  7. Fowler CJ, Callingham BA, Mantle TJ, Tipton KF (1978) Monoamine oxidase A and B: a useful concept? Biochem Pharmacol 27:97–101Google Scholar
  8. Fowler CJ, Oreland L, Callingham BA (1981) The acetylenic monoamine oxidase inhibitors clorgyline, deprenyl, pargyline and J-508: their properties and applications. J Pharm Pharmacol 33:341–347Google Scholar
  9. Fuller RW (1968) Influence of substrate in the inhibition of rat liver and brain monoamine oxidase. Arch Int Pharmacodyn 174:32–36Google Scholar
  10. Hellman B (1965) Studies in obese-hyperglycemic mice. Ann N Y Acad Sci 131:541–558Google Scholar
  11. Houslay MD, Tipton KF (1974) A kinetic evaluation of monoamine oxidase activity in rat liver mitochondrial outer membranes. Biochem J 139:645–652Google Scholar
  12. Houslay MD, Tipton KF (1976) Multiple forms of monoamine oxidase: fact and artefact. Life Sci 19:467–478Google Scholar
  13. Johnston JP (1968) Some observations upon a new inhibitor of monoamine oxidase in brain tissue. Biochem Pharmacol 17:1285–1297Google Scholar
  14. Knoll J (1980) Monoamine oxidase inhibitors: chemistry and pharmacology. In: Sandler M (ed) Enzyme inhibitors as drugs. Macmillan Press, London, pp 151–171Google Scholar
  15. Knoll, J, Magyar K (1972) Some puzzling pharmacological effects of monoamine oxidase inhibitors. Adv Biochem Psychopharmacol 5:393–408Google Scholar
  16. Lacy PE, Kostianovsky M (1967) Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 16:35–39Google Scholar
  17. Lenke D, Gries J, Kretzschmar R (1981) Pharmacology of amezinium, a novel antihypotensive drug. III. Studies on the mechanism of action. Arzneimittelforsch 31:1558–1565Google Scholar
  18. Lenzen S (1979) Insulin secretion by isolated perfused rat and mouse pancreas. Am J Physiol 236:E391-E400Google Scholar
  19. Lenzen, S, Nahrstedt H (1983) Characterization of pancreatic islet monoamine oxidase. Naunyn-Schmiedeberg's Arch Pharmacol 322:R57Google Scholar
  20. Lenzen S, Panten U (1983) Characterization of succinate dehydrogenase and α-glycerophosphate dehydrogenase in pancreatic islets. Biochem Med (in press)Google Scholar
  21. Lenzen S, Formanek H, Panten U (1982) Signal function of metabolism of neutral amino acids and 2-keto acids for initiation of insulin secretion. J Biol Chem 257:6631–6633Google Scholar
  22. Mantle TJ, Wilson K, Long RF (1975) Studies on the selective inhibition of membrane-bound rat liver monoamine oxidase. Biochem Pharmacol 24:2031–2038Google Scholar
  23. McKnight GS (1977) A colorimetric method for the determination of submicrogram quantities of protein. Anal Biochem 78:86–92Google Scholar
  24. Neff NH, Yang H-YT (1974) Another look at the monoamine oxidases and the monoamine oxidase inhibitor drugs. Life Sci 14:2061–2074Google Scholar
  25. Steppeler A, Starke K (1980) Selective inhibition by amezinium of intraneuronal monoamine oxidase. Nauyn-Schmiedeberg's Arch Pharmacol 314:13–16Google Scholar
  26. Steppeler A, Pfändler R, Hedler L, Starke K (1980) An analysis of the effects of amezinium on postganglionic sympathetic neurones. Naunyn-Schmiedeberg's Arch Pharmacol 314:1–11Google Scholar
  27. Traut N, Brode E, Hoffmann HD (1981) Pharmacology of amezinium, a novel antihypotensive drug. IV. Biochemical investigations of the mechanism of action. Arzneimittelforsch 31:1566–1574Google Scholar
  28. Wurtman RJ, Axelrod J (1963) A sensitive and specific assay for the estimation of monoamine oxidase. Biochem Pharmacol 12:1439–1441Google Scholar

Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • S. Lenzen
    • 1
  • H. Nahrstedt
    • 1
  • U. Panten
    • 1
  1. 1.Institut für Pharmakologie und ToxikologieUniversität GöttingenGöttingenGermany

Personalised recommendations