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The effect of selective type A or type B monoamine oxidase inhibition on the intrasynaptosomal deamination of (3H)serotonin in rat spinal cord tissue

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Summary

The degree to which the type A and type B forms of monoamine oxidase participate in the intraneuronal deamination of (3H)serotonin (5-HT) was examined in synaptosomal-rich fractions of rat spinal cord tissue. Synaptosomes were labeled with (3H)5-HT and superfused with physiological buffers containing selective concentrations of a type A (clorgyline) or a type B (deprenyl) MAO inhibitor. The efflux of (3H)5-HT and newly-formed (3H)5-hydroxyindoleacetic acid (5-HIAA) was determined and compared to controls over time. In control samples, a slight decline in (3H)5-HT efflux occurred over the experimental superfusion period. However, a stable formation and efflux of (3H)5-HIAA was seen during this same period of time. When clorgyline was added to the superfusion buffer, a rapid decline in superfusate levels of (3H)5-HIAA was observed. Similar experiments in the presence of deprenyl were without effect. In order to elevate cytoplasmic concentrations of (3H)5-HT and therefore increase its chances for interaction with nerve terminal MAO, reserpine was added to the superfusion buffer. Reserpine caused a greater than 3-fold increase in (3H)5-HIAA formation with no change in (3H)5-HT efflux. Clorgyline inhibited this increase in (3H)5-HIAA formation but deprenyl was again without effect. In the presence of clorgyline, reserpine also caused an increase in (3H)5-HT efflux. These results strongly support the notion that 5-HT deamination within rat spinal cord nerve terminals occurs primarily, if not exclusively, through an interaction with type A MAO.

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Abbreviations

5-HT:

5-hydroxytryptamine, serotonin

MAO:

monoamine oxidase

5-HIAA:

5-hydroxyindoleacetic acid

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Authors and Affiliations

  1. Department of Anesthesiology, West Virginia University Medical Center/Health Sciences Center, 26506, Morgantown, West Virginia, USA

    J. B. Amedro, L. M. Brown, D. J. Smith & G. M. Williams

  2. Department of Behavioral Medicine/Psychiatry, West Virginia University Medical Center/Health Sciences Center, 26506, Morgantown, West Virginia, USA

    A. J. Azzaro

  3. Department of Neurology, West Virginia University Medical Center/Health Sciences Center, 26506, Morgantown, West Virginia, USA

    A. J. Azzaro

  4. Department of Pharmacology/Toxicology, West Virginia University Medical Center/Health Sciences Center, 26506, Morgantown, West Virginia, USA

    A. J. Azzaro, L. M. Brown, D. J. Smith & G. M. Williams

Authors
  1. A. J. Azzaro
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  2. J. B. Amedro
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  3. L. M. Brown
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  4. D. J. Smith
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  5. G. M. Williams
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Additional information

Supported in part by N.I.H. grants GM 30002, 5-T32-GM 07039, and the West Virginia University Medical Corporation. L. M. B. was supported by a Swiger Fellowship

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Azzaro, A.J., Amedro, J.B., Brown, L.M. et al. The effect of selective type A or type B monoamine oxidase inhibition on the intrasynaptosomal deamination of (3H)serotonin in rat spinal cord tissue. Naunyn-Schmiedeberg's Arch Pharmacol 338, 9–13 (1988). https://doi.org/10.1007/BF00168805

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  • DOI: https://doi.org/10.1007/BF00168805

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