AJP - Gastrointestinal and Liver Physiology, Vol 255, Issue 5 566-G570, Copyright © 1988 by American Physiological Society
Ketocyclazocine, a kappa-opioid receptor agonist, and control of intestinal myoelectric activity in dogs
G. L. Telford, A. Caudill, R. E. Condon and J. H. Szurszewski
Department of Surgery, Clement J. Zablocki Veterans Administration Medical Center, Milwaukee 53295.
The role of kappa-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 less than 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 less than 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 less than 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 kappa-opioid receptors may play
a role in the inhibition of gastric action potentials and small intestinal
spiking activity.
