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The enteric neural receptor for 5-hydroxytryptamine.

M D Gershon, M Takaki, H Tamir

    Experientia
    |July 15, 1985
    PubMed
    Summary
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    Researchers identified a novel serotonin (5-HT) receptor in the enteric nervous system. This neural receptor differs from central nervous system 5-HT receptors and is a potential target for new therapeutics.

    Area of Science:

    • Neuroscience
    • Gastroenterology
    • Pharmacology

    Background:

    • Serotonin (5-HT) plays a crucial role in regulating gastrointestinal function.
    • The specific neural receptors mediating 5-HT's actions within the enteric nervous system (ENS) are not fully characterized.

    Purpose of the Study:

    • To characterize the specific serotonin (5-HT) receptor present in the enteric nervous system.
    • To investigate the pharmacological properties and localization of this enteric 5-HT receptor.
    • To identify potential novel antagonists for this receptor.

    Main Methods:

    • Radioligand binding assays using 3H-5-HT on isolated enteric membranes.
    • Radioautography to visualize 3H-5-HT binding sites.
    • Intracellular recordings from myenteric plexus ganglion cells.

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  • Pharmacological characterization using various neurotransmitter antagonists and analogues.

    • Main Results:

    • High-affinity, saturable, and specific binding of 3H-5-HT was demonstrated in enteric membranes and myenteric ganglia.
    • Binding sites were localized to myenteric ganglia and the mucosal-submucosal interface.
    • A novel 5-HT antagonist, 5-HTP-DP, was identified, which selectively antagonized 5-HT's action on enteric neurons without affecting other neurotransmitters.
    • The pharmacology of the enteric 5-HT receptor matched that of M or neural 5-HT receptors and differed from CNS 5-HT receptors.

    Conclusions:

    • The study successfully characterized a distinct enteric neural serotonin (5-HT) receptor.
    • These enteric 5-HT receptors are pharmacologically different from those found in the central nervous system.
    • The novel antagonist 5-HTP-DP provides a valuable tool for further research and potential therapeutic development targeting the ENS.