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

Melatonin is synthesized during the night by the pineal gland. Recently, me latonin binding sites have been identified in the gut. Despite few studies, the physiological role of melatonin in gut function remains unclear. The o bjective of the present study was to investigate the effects of melatonin i n the regulation of intestinal motility by using the melatonin receptor ant agonist S 22153 in rats. Twenty-four male Wistar rats (400 +/- 25 g) were e quipped with intraparietal electrodes along the small intestine. Rats were subjected to a 12:12 hr light:dark schedule. During the dark phase, intesti nal migrating motor complexes (MMCs) frequency increased (P < 0.05) by 20% in the duodenum and in the jejunum compared with daylight. This effect is d ue to a significant reduction in the irregular spiking activity (ISA) of MM Cs. 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 ad ministration of S 22153 (2 mg/kg sc) at night suppressed these nocturnal va riations and restored the daylight values. In contrast, S 22153 was ineffec tive during daylight whatever the digestive state. Administration of melato nin (1 mg/kg iv) during the preprandial state, 3 hr after light onset, decr eased (-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 mo tor profile in the entire small intestine. In contrast, when administered a t the end of the meal it was ineffective. Preprandial and postprandial mela tonin effects were prevented by S 22153 pretreatment. In conclusion, these findings reveal, first, that endogenous melatonin is physiologically involv ed in the pre- and postprandial changes of intestinal motility at night. Se cond, exogenous melatonin produces pharmacological effects on pre- and post prandial intestinal motility. In both cases, the action of melatonin corres ponds to an inhibition of ISA and a reinforcement of the cyclic MMC pattern .