Effect of melatonin on motility pattern of small intestine in rats and its inhibition by melatonin receptor antagonist S 22153

Abstract

Melatonin is synthesized during the night by the pineal gland. Recently, melatonin binding sites have been identified in the gut. Despite few studies, the physiological role of melatonin in gut function remains unclear. The objective of the present study was to investigate the effects of melatonin in the regulation of intestinal motility by using the melatonin receptor antagonist S 22153 in rats. Twenty-four male Wistar rats (400 +/- 25 g) were equipped with intraparietal electrodes along the small intestine. Rats were subjected to a 12:12 hr light:dark schedule. During the dark phase, intestinal migrating motor complexes (MMCs) frequency increased (P < 0.05) by 20% in the duodenum and in the jejunum compared with daylight. This effect is due to a significant reduction in the irregular spiking activity (ISA) of MMCs. Concurrently, at night, the duration of the postprandial motor response is reduced by 30% in the duodenum and 50% in the jejunum and ileum. The administration of S 22153 (2 mg/kg sc) at night suppressed these nocturnal variations and restored the daylight values. In contrast, S 22153 was ineffective during daylight whatever the digestive state. Administration of melatonin (1 mg/kg iv) during the preprandial state, 3 hr after light onset, decreased (-80%) the duration of the ISA of MMCs at the three intestinal levels. During the satiety phase, melatonin administered 10 min before or 15 min after food onset induced the appearance of a transitory preprandial-like motor profile in the entire small intestine. In contrast, when administered at the end of the meal it was ineffective. Preprandial and postprandial melatonin effects were prevented by S 22153 pretreatment. In conclusion, these findings reveal, first, that endogenous melatonin is physiologically involved in the pre- and postprandial changes of intestinal motility at night. Second, exogenous melatonin produces pharmacological effects on pre- and postprandial intestinal motility. In both cases, the action of melatonin corresponds to an inhibition of ISA and a reinforcement of the cyclic MMC pattern.

Peripheral melatonin mediates neural stimulation of duodenal mucosal bicarbonate secretion

“…Recent studies in rats have shown that during the dark phase, compared with daylight phase, the frequency of duodenal and jejunum intestinal migrating motor complexes was increased by 20% and that this was abolished by the melatonin antagonist S22153 (32). These authors concluded that pineal gland melatonin is involved in the dark-phase physiological control of the pre-and postprandial changes of intestinal motility.…”

Melatonin Attenuates Noise Stress-induced Gastrointestinal Motility Disorder and Gastric Stress Ulcer: Role of Gastrointestinal Hormones and Oxidative Stress in Rats

“…56 MT is reported to inhibit irregular spiking activity and reinforces the cyclic MMC pattern. 57 These results suggest that MT affects GI motility in rats, which might be mediated by MT receptors in the GI tract, although central receptors for the hormone is possibly involved. 58 Results of lots of articles suggest that CGRP plays an important role in the pathogenesis of gastric ulcer 45,47,59 and GI motility disorder.…”

Localization, Physiological Significance and Possible Clinical Implication of Gastrointestinal Melatonin

“…In rats, an endogenous melatonin produced a pharmacological effect on pre-and postprandial intestinal motility. The effect, the inhibition of irregular spiking activity and a reinforcement of the migrating motor complexes, was observed only at night, when melatonin levels in blood are high [126].…”