Ketocyclazocine, a κ-opioid receptor agonist, and control of intestinal myoelectric activity in dogs

The role of κ-opioid receptors in the control of fed and fasted myoelectrical activity of the stomach and small intestine was studied in conscious dogs implanted with bipolar silver electrodes. In fasted dogs, migrating myoelectric complex (MMC) cycle times were 105 ± 14 min in the duodenum. Administration of ketocyclazocine (1 mg/kg iv) inhibited contractile activity, blocked migration of distally propagating MMCs, and increased the MMC cycle time to 246 ± 56 min (P < 0.0005). Pretreatment with naloxone (2 mg/kg iv) 5 min before administration of ketocyclazocine (1 mg/kg iv) prevented the disruption by ketocyclazocine of the distally propagating MMC but did not completely antagonize the effect of ketocyclazocine on MMC cycle time. MMC cycle time was 102 ± 14 min before naloxone plus ketocyclazocine administration and 138 ± 22 min after administration (P < 0.005). Although MMC cycle times were still significantly prolonged over control after naloxone plus ketocyclazocine, cycle times were significantly decreased compared with ketocyclazocine administration alone (P < 0.005). Ketocyclazocine (1 mg/kg iv) completely inhibited the fed pattern of myoelectric activity for 74 ± 26 min when administered 15 min after feeding. Bethanecol (2 mg sc)-initiated spike activity was not blocked by ketocyclazocine. These studies suggest that endogenous opioids and κ-opioid receptors may play a role in the inhibition of gastric action potentials and small intestinal spiking activity.