Melatonin as a modulator of the ileal brake mechanism

The gastrointestinal tract represents the most important extrapineal source of melatonin. Intestinal melatonin release is induced by the ileal passage of nutrients and could play a part in the control of postprandial gut motility. The specific aim of this study was to determine the putative role of melatonin in the "ileal brake" reflex, an important mechanism released by ileal lipids that regulates the gastric emptying of chyme.

Under general anaesthesia rats were fitted with ileal cannula exteriorized at the back of the neck. After a 1-week recovery, experiments were performed in conscious fasted animals. Rats were fed by gavage 1.5 ml casein hydrolyse plus 0.05% phenol red and either saline or Intralipid were continuously infused (2 ml/h) into the ileum. Gastric emptying was measured 50 min after ingestion by gastric lavage and determination of phenol red by spectrophotometry. The effects of melatonin (1 mg/kg) and melatonin antagonist S-22153 (dose-response study 0.2-25 mg/kg) were tested versus vehicle in paired experiments at 1-week intervals.

Ileal infusion of lipids delayed gastric emptying. During ileal infusion of lipids, melatonin antagonist S-22153, but not melatonin, potentiated the delay in gastric emptying induced by the ileal brake mechanism. The inhibition of gastric emptying induced by S-22153 was dose related. Neither melatonin nor S-22153 had noticeable effects on gastric emptying during ileal infusion of saline.

Our data suggest that melatonin, released in response to ileal lipids, exerts a modulatory influence that decreases the inhibitory effects of the ileal brake on gastric emptying of nutrients.