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. 1980 Jun;69(2):215–225. doi: 10.1111/j.1476-5381.1980.tb07893.x

The relationship between nerve terminal adenosine triphosphatases and neurotransmitter release: as determined by the use of antidepressant and other CNS-active drugs.

J C Gilbert, M G Wyllie
PMCID: PMC2044255  PMID: 6108138

Abstract

1 The role of adenosine triphosphatases (ATPases) in neurotransmitter release was studied using nerve terminals (synaptosomes) prepared from rat cerebral cortex as a model. 2 Amitriptyline, nortriptyline, protriptyline, desipramine and imipramine were found to inhibit ATPases at concentrations of 10(-5) M and above. The drugs inhibited both the basal and electrically evoked release of acetylcholine (ACh) and noradrenaline (NA) at concentrations of 10(-4) M and above. 3 At low concentrations of antidepressants (10(-8) and 10(-7) M) release of NA was enhanced but there was no effect on ACh release. 4 Other drugs which inhibit Na+, K+-ATPase increase basal NA release as did drugs which inhibited vesicular MG2+-ATPase. 5 A model is proposed suggesting that transmitter release/re-uptake depends on (1) active Na+, K+-ATPase at the presynaptic membrane and (2) an active synaptic vesicular MG2+-ATPase.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BONTING S. L., SIMON K. A., HAWKINS N. M. Studies on sodium-potassium-activated adenosine triphosphatase. I. Quantitative distribution in several tissues of the cat. Arch Biochem Biophys. 1961 Dec;95:416–423. doi: 10.1016/0003-9861(61)90170-9. [DOI] [PubMed] [Google Scholar]
  2. Caratsch C. G., Waser P. G. Tricyclic antidepressants: action on synaptosomal acetylcholinesterase and ATPase in the brain of guinea pigs and subcellular distribution. Neuropharmacology. 1973 Jun;12(6):563–575. doi: 10.1016/0028-3908(73)90006-3. [DOI] [PubMed] [Google Scholar]
  3. Corbett L., Christian S. T., Monti J. A., McClain L. D. Inhibition of synaptic vesicular Mg+2 dependent ATPase ('stenin') by antipsychotic phenothiazines. Res Commun Chem Pathol Pharmacol. 1974 Aug;8(4):607–614. [PubMed] [Google Scholar]
  4. GRAY E. G., WHITTAKER V. P. The isolation of nerve endings from brain: an electron-microscopic study of cell fragments derived by homogenization and centrifugation. J Anat. 1962 Jan;96:79–88. [PMC free article] [PubMed] [Google Scholar]
  5. Garcia A. G., Kirpekar S. M. Letter: Inhibition of Na, K-activated ATPase and release of neurotransmitters. Nature. 1975 Oct 23;257(5528):722–722. doi: 10.1038/257722b0. [DOI] [PubMed] [Google Scholar]
  6. Garcia A. G., Kirpekar S. M. Release of noradrenaline from slices of cat spleen by pre-treatment with calcium, strontium and barium. J Physiol. 1973 Dec;235(3):693–713. doi: 10.1113/jphysiol.1973.sp010411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Garcia A. G., Kirpekar S. M. Release of noradrenaline from the cat spleen by sodium deprivation. Br J Pharmacol. 1973 Apr;47(4):729–747. doi: 10.1111/j.1476-5381.1973.tb08200.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gilbert J. C., Allen J. M., Townsend B. G., Wyllie M. G. Drugs affecting the central nervous system: effects of pemoline and tricyclic antidepressants on nerve terminal adenosine triphosphatase activities and neurotransmitter release. Neuropharmacology. 1978 Jun;17(6):419–421. doi: 10.1016/0028-3908(78)90017-5. [DOI] [PubMed] [Google Scholar]
  9. Gilbert J. C., Davison D. V., Wyllie M. G. Studies of the physiological roles of prostaglandins in the central nervous system. Neuropharmacology. 1978 Jun;17(6):417–419. doi: 10.1016/0028-3908(78)90016-3. [DOI] [PubMed] [Google Scholar]
  10. Gilbert J. C., Wyllie M. G., Davison D. V. Nerve terminal ATPase as possible trigger for neurotransmitter release. Nature. 1975 May 15;255(5505):237–238. doi: 10.1038/255237a0. [DOI] [PubMed] [Google Scholar]
  11. Gilbert J. C., Wyllie M. G. Effects of anticonvulsant and convulsant drugs on the ATPase activities of synaptosomes and their components. Br J Pharmacol. 1976 Jan;56(1):49–57. doi: 10.1111/j.1476-5381.1976.tb06958.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gilbert J. C., Wyllie M. G. Synaptosome transmitter release and ATPase activity [proceedings]. Br J Pharmacol. 1977 Jun;60(2):300P–301P. [PMC free article] [PubMed] [Google Scholar]
  13. Hosie R. J. The localization of adenosine triphosphatases in morphologically characterized subcellular fractions of guinea-pig brain. Biochem J. 1965 Aug;96(2):404–412. doi: 10.1042/bj0960404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kirshner N. Functional organization of adrenal chromaffin vesicles. Adv Biochem Psychopharmacol. 1975;13:95–107. [PubMed] [Google Scholar]
  15. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  16. Lai J. C., Clark J. B. Preparation and properties of mitochondria derived from synaptosomes. Biochem J. 1976 Feb 15;154(2):423–432. doi: 10.1042/bj1540423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lai J. C., Walsh J. M., Dennis S. C., Clark J. B. Synaptic and non-synaptic mitochondria from rat brain: isolation and characterization. J Neurochem. 1977 Mar;28(3):625–631. doi: 10.1111/j.1471-4159.1977.tb10434.x. [DOI] [PubMed] [Google Scholar]
  18. Matthaei H., Lentzen H., Philippu A. Competition of some biogenic amines for uptake into synaptic vesicles of the striatum. Naunyn Schmiedebergs Arch Pharmacol. 1976;293(1):89–96. doi: 10.1007/BF00498875. [DOI] [PubMed] [Google Scholar]
  19. Nag D., Ghosh J. J. Imipramine-induced changes of brain adenosine triphosphatase activity. The role of spermine in counteracting the disorganizing effect of the drug on membrane ATPase. J Neurochem. 1973 Apr;20(4):1021–1027. doi: 10.1111/j.1471-4159.1973.tb00073.x. [DOI] [PubMed] [Google Scholar]
  20. O'Hanlon J. F., Jr, Campuzano H. C., Horvath S. M. A fluorometric assay for subnanogram concentrations of adrenaline and noradrenaline in plasma. Anal Biochem. 1970 Apr;34(2):568–581. doi: 10.1016/0003-2697(70)90142-9. [DOI] [PubMed] [Google Scholar]
  21. Paton W. D., Vizi E. S., Zar M. A. The mechanism of acetylcholine release from parasympathetic nerves. J Physiol. 1971 Jul;215(3):819–848. doi: 10.1113/jphysiol.1971.sp009500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Toll L., Gundersen C. B., Jr, Howard B. D. Energy utilization in the uptake of catecholamines by synaptic vesicles and adrenal chromaffin granules. Brain Res. 1977 Nov 4;136(1):59–66. doi: 10.1016/0006-8993(77)90131-7. [DOI] [PubMed] [Google Scholar]
  23. Vizi E. S. Stimulation, by inhibition of (Na + -K + -Mg 2+ )-activated ATP-ase, of acetylcholine release in cortical slices from rat brain. J Physiol. 1972 Oct;226(1):95–117. doi: 10.1113/jphysiol.1972.sp009975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Whittaker V. P., Michaelson I. A., Kirkland R. J. The separation of synaptic vesicles from nerve-ending particles ('synaptosomes'). Biochem J. 1964 Feb;90(2):293–303. doi: 10.1042/bj0900293. [DOI] [PMC free article] [PubMed] [Google Scholar]

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