The Effect of an Opiate Receptor Antagonist on the Heal Brake Mechanism in the Rat

Abstract

Studies investigated the effect of the opiate antagonist naloxone (10 mg/kg) on stomach to caecum transit (SCTT) during ileal infusion of saline or Intralipid. SCTT of the head of the meal was measured by hydrogen analysis and meal distribution by the radiolabelled meal technique. Intralipid delayed SCTT by delaying both gastric emptying (p < 0.01) and small bowel transit. Naloxone did not affect SCTT during ileal saline infusion, but produced a distal shift (p < 0.05) in the geometric centre of the meal and increased radioactivity in the caecum (p < 0.001) 100 min after gavage. Naloxone abolished the delayed SCTT of the meal induced by ileal lipid infusion, with an associated increase in radioactivity in the caecum at 200 min (p < 0.01), although the geometric centre was shifted proximally within the intestine (p < 0.01). The results suggest that the ileal brake is mediated in part by endogenous opiate pathways.

Treatment of opioid-induced gut dysfunction

“…This observation is consistent with the ability of naloxone to reduce the intermittent periods of peristaltic inactivity observed during prolonged periods of distension [46][47][48]. Studies of the effects of naloxone in rats suggest that endogenous opioids contribute to the ileal brake of the stomach-to-caecum transit caused by ileal infusion of lipids [49].…”

The role of endogenous opioids in the control of gastrointestinal motility: predictions from in vitro modelling

“…The suggestion that endogenous opioids act to suppress intestinal motility as part of a ‘defensive’ mechanism against inappropriate or adverse conditions is supported by different studies in conscious rats, and also by studies in humans. In rats, naloxone only slightly increased normal stomach‐to‐caecum transit times; but when transit was slowed by ileal infusion of lipids, naloxone abolished this delay 33 . These experiments suggest that endogenous opioids contribute to the mechanism of the ‘ileal brake’, either directly or indirectly, through a modulation of the effects exerted on the enteric nervous system by mechanisms extrinsic to this system.…”

“…Together, these data also find some consistency with studies in conscious rats. Although naloxone had no significant effects on stomach‐to‐caecum transit times measured using a breath–hydrogen technique, there was a tendency for the drug to increase the amount of meal transported into the caecum when measured by radiolabelling the same meal 33 . In studies using flat sections of guinea‐pig colon, naloxone 1 µmol L −1 and 10 µmol L −1 were found to increase the descending relaxation (plus vasoactive intestinal peptide release) and ascending contraction reflexes evoked by radial stretch 34 .…”

“…Although naloxone had no significant effects on stomach-to-caecum transit times measured using a breath-hydrogen technique, there was a tendency for the drug to increase the amount of meal transported into the caecum when measured by radiolabelling the same meal. 33 In studies using flat sections of guinea-pig colon, naloxone 1 lmol L )1 and 10 lmol L )1 were found to increase the descending relaxation (plus vasoactive intestinal peptide release) and ascending contraction reflexes evoked by radial stretch. 34 However, when using more intact preparations, naloxone 0.1 lmol L )1 had no effect on the movements of endogenous faecal pellets in guinea-pig mid-to-distal colon 10 and naloxone 0.5 lmol L )1 had no effects on the peristaltic reflex in rat proximal colon (BR Tuladhar, unpublished).…”

“…In rats, naloxone only slightly increased normal stomach-to-caecum transit times; but when transit was slowed by ileal infusion of lipids, naloxone abolished this delay. 33 These experiments suggest that endogenous opioids contribute to the mechanism of the Ôileal brakeÕ, either directly or indirectly, through a modulation of the effects exerted on the enteric nervous system by mechanisms extrinsic to this system. Similarly, in healthy human volunteers, naloxone may not affect intestinal motility.…”