Blockade of Migrating Myoelectric Complexes by Naloxone

Abstract

Prior experiments in our laboratory have shown that morphine initiates migrating myoelectric complexes (MMECs) in the small intestine in both fed and fasted dogs. Because it was therefore possible that endogenous opioids and opioid receptors could be involved in the control of endogenously initiated MMECs, we studied the effects of the opioid receptor antagonist naloxone. Naloxone (1–2 mg/kg, I.V., then 0.2–1.0 mg/kg/hr I.V. for 2.5–5.5 hrs) starting 30 to 60 minutes after the initiation of an MMEC in the duodenum, blocked the initiation of MMECs in the duodenum in 6 of 8 dogs. In 3 of the 6 dogs where the initiation of duodenal MMECs was blocked, jejuno-ileal MMECs were initiated prior to the return of an MMEC in the duodenum. Cycle times on the duodenum for the 8 dogs average 105 ± 9 min (mean ± SEM) prior to the infusion of naloxone and 235 ± 31 min (mean ± SEM) during the infusion of the antagonist. Naloxone (2 mg/kg I.V.) did not block the initiation of MMECs by exogenously administered motilin (400–500 mg/kg I.V.) when motilin was administered 5 minutes after naloxone (2 mg/kg I.V.) (n=4). To investigate the possibility that naloxone had an atropine like effect and was blocking cholinergic receptors rather than opioid receptors, bethanechol (5 mg, subq.) (n=4) was administered during a standard naloxone infusion and during a saline infusion. There was a marked increase in spiking at all electrode sites with bethanechol with both the saline and naloxone infusions. In prior experiments we had demonstrated that this dose of naloxone completely blocked morphine’s effect on the electrical activity of the gastrointestinal tract. We conclude: 1) endogenous opioids and their receptors may play a role in the control of initiation of duodenal MMECs, and 2) motilin does not act via opioid receptors. (Supported by NIH Grants AM 00741 and AM 17238.)