Peripheral Neural 5-HT Receptors: Subtypes in the Enteric Nervous System

Abstract

Peripheral neural 5-hydroxytryptamine (5-HT) receptors have been analyzed in the enteric nervous system (ENS) and related to possible physiological actions of 5-HT. Receptors have been distinguished electrophysiologically, using intracellular microelectrodes, as well as by studies of the binding of specific radioligands. Radioligand binding was assessed both by rapid filtration of isolated membranes and by radioautography. Three subtypes of 5-HT receptor have been identified. 5-HT1P receptors mediate slow depolarizations of myenteric II/AH neurons associated with an increase in input resistance. These responses are blocked by dipeptides of 5-hydroxytryptophan and by BRL 24924 and they are mimicked by hydroxylated indalpines. 5-HT1P receptors can be labeled by 3H-5-HT and are located on neurons in the enteric plexuses and on the mucosal processes of intrinsic enteric neurons. Serotonergic EPSPs are mediated by these receptors and it is postulated that they may also be involved in initiation of the peristaltic reflex and in the regulation of gastric emptying. 5-HT3 receptors are responsible for fast depolarizations of myenteric and submucosal neurons associated with a fall in input resistance. These responses are blocked by ICS 205-930 and mimicked by 2-methyl-5-HT. 5-HT1A receptors mediate hyperpolarizing responses associated with a decrease in input resistance. These responses can be mimicked by 8-hydroxy-2(di-n-propyl-amino)tetralin (8-OH-DPAT). As yet no physiological role has been attributed to 5-HT3 or 5-HT1A receptors in the ENS.