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Chemical sympathectomy induced by 5.6-dihydroxytryptamine

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Summary

The effect of different doses of 5.6-dihydroxytryptamine—a serotonin analogue which produces a degeneration of serotonin containing nerve terminals in the rat brain—on the noradrenaline (NA) content and—storage sites of peripheral sympathetic nerves in the mouse and rat heart, spleen, rectum and vas deferens has been investigated by fluorescence—, electron microscopical and chemical methods. Moderate doses of 5.6-dihydroxytryptamine (5.6-DHT) (10–45 mg/kg ip.) cause a temporary, reversible displacement of noradrenaline from the adrenergic nerves concomitant with a significant increase in the number and opacity of small and especially large granular vesicles. The recovery of the neuronal NA concentration is, however, retarded after doses higher than 45 mg/kg (60 or 100 mg/kg ip.); a partial degeneration of varicose NA terminals is verified fluorescence- and electron microscopically. A combined treatment of animals with tyrosine hydroxylase inhibitors (α-methyl-paratyrosine or α-propyl-dopacetamide) and 5.6-DHT, in some instances also followed by reserpine, potentiates the destructive properties of 5.6-DHT; a similar potentiation is accomplished by reserpine posttreatment or by an additional pretreatment of animals with reserpine and nialamide.

The results suggest that 5.6-DHT when given in moderate doses (up to 45 mg/kg) may be handled by sympathetic adrenergic nerves like a false neurotransmitter which displaces noradrenaline from the stores, but that it causes a “chemical degeneration” of noradrenaline containing nerve terminals when applied either in single high doses (60 or 100 mg/kg ip.), or when administered in moderate non-degenerative doses together with drugs that impair the neuronal inactivation mechanisms for 5.6-DHT (granular uptake and storage mechanism and/or monoamine oxidase activity) and thus provoke a temporary increase in the amount of free 5.6-DHT in the neuron's cytoplasm.

The molar efficiency of 5.6-DHT in causing a chemical sympathectomy is clearly inferior to that caused by 6-hydroxydopamine. The differences are probably mainly due to differences in the affinity of both drugs to the amine uptake system located at the cell membrane and the membrane of the intraneuronal storage vesicles of the adrenergic nerve terminals.

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Authors and Affiliations

  1. Institute of Anatomy and Department of Neuroanatomy, Institute of Pharmacology, University of Hamburg, Germany

    H. G. Baumgarten, M. Göthert, A. F. Holstein & H. G. Schlossberger

  2. Max-Planck-Institute of Biochemistry, Munich, Germany

    H. G. Baumgarten, M. Göthert, A. F. Holstein & H. G. Schlossberger

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  1. H. G. Baumgarten
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  2. M. Göthert
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  3. A. F. Holstein
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  4. H. G. Schlossberger
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Supported by grants from the Deutsche Forschungsgemeinschaft.

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Baumgarten, H.G., Göthert, M., Holstein, A.F. et al. Chemical sympathectomy induced by 5.6-dihydroxytryptamine. Z.Zellforsch 128, 115–134 (1972). https://doi.org/10.1007/BF00306892

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