Serotonin Kompakt – Teil 1[*]

Zusammenfassung

Bereits in den 1960er-Jahren wurde eine Beteiligung von Serotonin (5-Hydroxytryptamin, 5-HT) an psychischen Krankheiten erkannt, was durch unterschiedlichste Forschungsansätze in den folgenden Jahren weiter untermauert werden konnte. Das Indolamin 5-HT wird zu den Monoamintransmittern gezählt und befindet sich in den serotonergen Neuronen (Raphe-Nuclei) des Hirnstamms sowie peripher hauptsächlich im Gastrointestinaltrakt und der Zirbeldrüse. 5-HT ist bei unterschiedlichstem kognitiven, emotionalen und autonomen Verhalten und bei zirkadianen Rhythmen beteiligt. Zusätzlich zu seiner Bedeutung als Neurotransmitter kommt 5-HT, das einem exakt geregelten Expressionsmuster unterliegt, eine wichtige Rolle während der pränatalen Entwicklung und auch in der adulten Neurogenese zu. Seine zahlreichen physiologischen und pathophysiologischen Effekte vermittelt 5-HT über spezifische prä- und postsynaptische 5-HT-Rezeptoren, deren Vorkommen und Wirkung hier näher ausgeführt werden. Der Serotonin-Transporter (SERT), der nach Ausschüttung des Botenstoffs in den synaptischen Spalt 5-HT aktiv in die Zelle zurücktransportiert, spielt nicht nur eine wichtige Rolle bei der Terminierung der serotonergen Neurotransmission, sondern ist auch ein wichtiges Angriffsziel für Antidepressiva. In diesem ersten Teil des Übersichtsartikels wird detailliert auf die neurobiologischen Grundlagen von 5-HT-Synthese, -Abbau und -Speicherung sowie die serotonerge Neurotransmission und die damit verbundenen physiologischen Effekte eingegangen, während der zweite Teil klinische Befunde näher erläutert und kritisch diskutiert.

Abstract

As soon as in the 1960’s, the role of serotonin (5-Hydroxytryptamin, 5-HT) in psychiatric disorders was realized, which was further substantiated by several lines of evidence amounting to a huge body of knowledge. The indolamine 5-HT belongs to the class of monoamine transmitters and can be found in the serotonergic neurons of the raphe nuclei in the brain stem. In the periphery, it is mainly present in the gastrointestinal system and the pineal gland. 5-HT is implicated in a variety of cognitive, emotional and vegetative behaviors, as well as in the regulation of circadian rhythms. Apart from its role as a neurotransmitter, it has an important function in prenatal development, where its expression pattern is tightly regulated, and in adult neurogenesis. The numerous effects of 5-HT are mediated by specific pre- and postsynaptic receptors, whose localization and functions are further described here. The serotonin transporter (SERT), which accomplishes the re-uptake of 5-HT into the neuron following its release in the synaptic cleft, not only has an important role in the termination of serotonergic neurotransmission but is also an important drug target for antidepressant compounds. In this part of the review, the neurobiological underpinnings of 5-HT synthesis, metabolism, and neurotransmission as well as the corresponding physiological consequences are summarized, while in the second part, an overview on clinical findings is provided and critically discussed.

Schlüsselwörter

Neurotransmitter - Metabolismus - Entwicklung - Physiologie - Serotonin-Transporter

Keywords

neurotransmitter - metabolism - development - physiology - serotonin transporter

1 Die dieser Arbeit zugrunde liegenden Untersuchungen wurden durch die DFG (GK-1156, an CK und KPL, RE1632/1-5 an AR, KFO 125 an AR und KPL; SFB 581 an AS und KPL, SFB TRR 58 an AR und KPL), das BMBF (IZKF Würzburg, 01KS9603, an KPL; IZKF N-27-N, an AR) und die EU (NEWMOOD LSHM-CT-2003-503474, an KPL) gefördert.

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1 Die dieser Arbeit zugrunde liegenden Untersuchungen wurden durch die DFG (GK-1156, an CK und KPL, RE1632/1-5 an AR, KFO 125 an AR und KPL; SFB 581 an AS und KPL, SFB TRR 58 an AR und KPL), das BMBF (IZKF Würzburg, 01KS9603, an KPL; IZKF N-27-N, an AR) und die EU (NEWMOOD LSHM-CT-2003-503474, an KPL) gefördert.