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The enteric neural receptor for 5-hydroxytryptamine

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Summary

An enteric neural receptor for serotonin (5-HT) has been characterized. This receptor was assayed, using3H-5-HT as a radiologand, by rapid filtration of isolated enteric membranes and by radioautography. In addition, intracellular recordings were made from ganglion cells of the myenteric plexus. High affinity, saturable, reversible, and specific binding of3H-5-HT was demonstrated both to membranes of the dissected longitudinal muscle with adherent myenteric plexus and the mucosa-submucosa. Radioautographs showed these3H-5-HT binding sites to be in myenteric ganglia and in a broad unresolved band at the mucosal-submucosal interface. Antagonists active at receptors for other neurotransmitters than 5-HT, at either of the two known types of CNS 5-HT receptor, and at 5-HT uptake sites on serotonergic neurons failed to inhibit binding of3H-5-HT. The structural requirements of analogues for binding to the enteric 5-HT receptor matched the known pharmacology of M or neural 5-HT receptors. A novel 5-HT antagonist was found. This compound, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP), antagonized the action of 5-HT on type II/AH cells of the myenteric plexus but did not affect the release or actions of acetylcholine (nicotinic or muscarinic) or substance P. 5-HTP-DP was also an equally potent displacer of3H-5-HT from its binding sites on enteric membranes. It is concluded that the sites responsible for specific binding of3H-5-HT are enteric M or neural 5-HT receptors. These receptors differ from those now known to be present in the CNS.

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Authors and Affiliations

  1. Departments of Anatomy and Cell Biology and Psychiatry, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, 10032, New York, New York, USA

    M. D. Gershon, M. Takaki, H. Tamir & T. Branchek

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  1. M. D. Gershon
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  2. M. Takaki
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  3. H. Tamir
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  4. T. Branchek
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Gershon, M.D., Takaki, M., Tamir, H. et al. The enteric neural receptor for 5-hydroxytryptamine. Experientia 41, 863–868 (1985). https://doi.org/10.1007/BF01970002

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