Serotonin: its role and receptors in enteric neurotransmission

Enteric neural 5-HT receptors were analyzed and related to possible physiological actions of 5-HT. Receptors were identified electrophysiologically with intracellular microelectrodes and by studies of the binding of radioligands. Radioligand binding was assessed by rapid filtration and by radioautography. Three subtypes of 5-HT receptor, 5-HT1P, 5-HT3, and 5-HT1A, were identified. 5-HT1P receptors were found to mediate slow depolarizations of myenteric neurons that were associated with a decrease in membrane conductance. These responses were inhibited by 5-HTP-DP and by BRL 24924 and mimicked by 5- and 6-hydroxyindalpine. 5-HT1P receptors were labeled with high affinity by 3H-5-HT and were located on both submucosal and myenteric neurons and on processes of intrinsic neurons in the lamina propria. Serotonergic EPSPs were found to be mediated by 5-HT1P receptors; it is postulated that 5-HT1P receptors may be involved in initiation of the peristaltic reflex and in the regulation of gastic emptying. 5-HT3 receptors have been shown to be responsible for fast depolarizations of myenteric and submucosal neurons associated with a rise in membrane conductance. These responses are antagonized by ICS 205-930 and mimicked by 2-methyl-5-HT. 5-HT1A receptors have been reported by others to mediate hyperpolarizing responses of myenteric neurons associated with a rise in membrane conductance. Hyperpolarizing responses are also elicited by the 5-HT1A agonist, 8-OH-DPAT. No physiological role has yet been identified for 5-HT3 or 5-HT1A receptors in the ENS.