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Über die Bedeutung des Serotonins im Fettgewebe

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Summary

1. Experiments in rats have shown that the interscapular fat as well as the epididymal fat contains relatively large amounts of serotonin (13 to 16 μg/g protein), and enzymes of serotonin formation and degradation. In addition, interscapular fat contains tyrosine-transaminase activity but no measurable tryptophane-pyrrolase activity nor activity of microsomal enzymes (degradation of hexobarbital).

The serotonin content of adipose tissue increased after blockade of monoamine oxidase (Pargyline, Nialamide) or injection of 5-hydroxytryptophane, and was reduced by treatment with reserpine.

2. Denervation depleted interscapular fat of norepinephrine but did not alter its serotonin and histamine content, while treatment with compound 48/80 markedly reduced the serotonin and histamine content without affecting the norepinephrine concentration of the tissue. These results indicate that in adipose tissue norepinephrine is stored in postganglionic neurons while serotonin as well as histamine is predominantly located in mast cells of this tissue.

The tyramine-induced lipolysis was inhibited by pretreatment with compound 48/80. However, dexamethasone restored the lipolytic effect of tyramine without affecting the decreased level of serotonin and histamine in the tissue.

3. On isolated epididymal fat pads of rats, serotonin (3 × 10−3 M) was ineffective in promoting lipolysis. If, however, monoamine oxidase was blocked by preincubation with pargyline, serotonin concentrations as low as 3 × 10−6 M had a significant lipolytic effect. This action of serotonin was further enhanced by additional blockade of phosphodiesterase by theophylline. Similar to norepinephrine, the lipolytic effect of serotonin was readily inhibited by low concentrations (1 × 10−6 M) of the β-adrenolytic Kö 592, but was not affected by depletion of the norepinephrine content of the fat pads (pretreatment with syrosingopine). 5-Hydroxyindole acetic acid, the end product of the metabolism of serotonin, had no inhibitory effect upon serotonin-induced lipolysis in concentrations up to 10−3 M.

Monoamine oxidase in epididymal fat deaminated serotonin several times more rapidly than dopamine or norepinephrine. This may explain the lack of lipolytic potency of serotonin in tissues with uninhibited monoamine oxidase.

The results indicate that the lipolytic action of serotonin is brought about in similar manner than that of catecholamines, i.e., by stimulation of adenylcyclase and a subsequent formation of cyclic adenosine-3′,5′-monophosphate (3,5-AMP) which in turn activates triglyceride lipase in adipose tissue.

Zusammenfassung

1. Versuche an Ratten haben ergeben, daß das interscapuläre und epididymale Fettgewebe relativ große Mengen Serotonin (13–16 μg/g Protein) sowie Enzyme der Serotoninbildung und des Serotoninabbaus enthält. Im interscapulären Fettgewebe ließ sich außerdem Tyrosin-Transaminase, jedoch keine Tryptophan-Pyrrolase und keine Hexobarbital-abbauenden Mikrosomenenzyme nachweisen.

Durch Injektion von 5-Hydroxytryptophan oder Hemmung der Monoaminoxydase (Pargylin, Nialamid) ließ sich der Serotoningehalt des Fettgewebes erhöhen, durch Injektion von Reserpin erniedrigen.

2. Denervierung verarmte das interscapuläre Fettgewebe an Noradrenalin, nicht aber an Serotonin oder Histamin. Demgegenüber verminderte die Injektion von Compound 48/80 den Serotonin- und Histamingehalt des Fettgewebes, hatte aber keinen Einfluß auf seinen Noradrenalingehalt.

Die indirekte lipolytische Wirkung des Tyramins wurde durch Behandlung mit Compound 48/80 abgeschwächt; sie ließ sich durch Dexamethason, das den Amingehalt des Fettgewebes nicht veränderte, wieder restituieren.

3. Am isolierten epididymalen Fettgewebe der Ratte wirkte Serotonin schon in kleinen Konzentrationen (3 · 10−6 M) lipolytisch, wenn man seine oxydative Desaminierung verhinderte (Pargylin). Durch zusätzliche Hemmung der Phosphodiesterase (Theophyllin) wurde die lipolytische Wirkung des Serotonins noch weiter verstärkt. Unter gleichen Versuchsbedingungen waren Dopamin zwanzigmal und Noradrenalin 400mal wirksamer. Die lipolytische Wirkung von Serotonin in Gegenwart von Pargylin und Theophyllin ließ sich, wie die lipolytische Wirkung von Noradrenalin, durch das β-Sympathicolyticum Kö 592 hemmen. Verarmung des Fettgewebes an Noradrenalin (Syrosingopin) hatte keinen Einfluß auf die lipolytische Wirkung des Serotonins. 5-Hydroxyindolessigsäure, das Abbauprodukt von Serotonin, hemmte die Serotoninwirkung nicht.

Die fehlende lipolytische Wirksamkeit des Serotonins bei intakter Monoaminoxydase könnte darauf beruhen, daß epididymales Fettgewebe Serotonin schneller desaminiert als Dopamin bzw. Noradrenalin.

Die Befunde sprechen dafür, daß Serotonin — ähnlich wie die Sympathicusstoffe — durch Stimulierung der Adenylcyclase (vermehrte Bildung von cyclischem Adenosin-3′,5′-Monophosphat) die Triglyceridlipase des Fettgewebes aktiviert.

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Authors and Affiliations

  1. Pharmakologisches Institut der Universität Frankfurt, Germany

    P. Bieck, K. Stock & E. Westermann

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  1. P. Bieck
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  2. K. Stock
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  3. E. Westermann
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Additional information

Herrn Professor Dr. P. Holtz zum 65. Geburtstag am 6.2. 1967 gewidmet.

Ausgeführt mit Unterstützung der Deutschen Forschungsgemeinschaft (We 272). Über einen Teil der Ergebnisse wurde auf der 28. Tagung der Deutschen Pharmakologischen Gesellschaft (Bieck u. Westermann), und auf dem 2. Internationalen Symposium über „Drugs Affecting Lipid Metabolism“ in Mailand (Westermann et al., 1967) berichtet, sowie in einer kurzen Mitteilung (Bieck et al., 1966).

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Bieck, P., Stock, K. & Westermann, E. Über die Bedeutung des Serotonins im Fettgewebe. Naunyn-Schmiedebergs Arch. Pharmak. u. Exp. Path. 256, 218–236 (1967). https://doi.org/10.1007/BF00539617

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