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pubmed:abstractText |
Serotonin (5-hydroxytryptamine, 5-HT) has been shown to be a neurotransmitter in the enteric nervous system (ENS). Although 5-HT is a mediator of slow excitatory postsynaptic potentials evoked by stimulation of interganglionic connectives, the precise role it plays in the physiology of the gut is unclear. Research has been hampered by an inadequate knowledge of the types of 5-HT receptor in the ENS and thus the lack of well-characterized antagonists. We now report the identification of two classes of enteric neural 5-HT receptor, the effects of activating these receptors on myenteric type II/AH neurons, and their characterization with specific agonists and antagonists. One class, which we propose to call 5-HT1P, is characterized by a high affinity for [3H]5-HT in radioligand binding assays. This class of receptor mediates a slow depolarization of myenteric type II/AH neurons associated with an increase in input resistance. Agonists at this receptor include, in addition to 5-HT (in order of potency), 5- and 6-hydroxyindalpine and 2-methyl-5-HT. 5-HT1P-mediated responses are specifically antagonized by 5-hydroxytryptophyl-5-hydroxytryptophan amide. The other class of 5-HT receptor, which we propose to call 5-HT2P, appears not to have a high affinity for [3H]5-HT. This receptor mediates a brief depolarization of myenteric II/AH neurons associated with a fall in input resistance. 2-Methyl-5-HT, at low concentrations, is a specific agonist at this receptor and ICS 205-930 is a specific antagonist. Binding of [3H]5-HT to enteric membranes is inhibited by 5-HT1P receptor agonists and antagonists but not by the 5-HT2P receptor antagonist ICS 205-930 or by MDL 72222, another compound reported to be an antagonist of 5-HT at peripheral receptors.
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