The enteric neural receptor for 5-hydroxytryptamine.
An enteric neural receptor for serotonin (5-HT) has been characterized. This receptor was assayed, using 3H-5-HT as a radioligand, 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 of 3H-5-HT was demonstrated both to membranes of the dissected longitudinal muscle with adherent myenteric plexus and the mucosa-submucosa. Radioautographs showed these 3H-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 of 3H-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 of 3H-5-HT from its binding sites on enteric membranes. It is concluded that the sites responsible for specific binding of 3H-5-HT are enteric M or neural 5-HT receptors. These receptors differ from those now known to be present in the CNS.
D006916:5-Hydroxytryptophan / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D004151:Dipeptides / Q000494:pharmacology; D007421:Intestine, Small / Q000294:innervation* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D011817:Rabbits; D011985:Receptors, Serotonin / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013329:Structure-Activity Relationship
D004151:Dipeptides; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; C022197:N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophanamide; D006916:5-Hydroxytryptophan