Inhibitory opioid receptors in canine pylorus

Abstract

In 18 anesthetized dogs, antroduodenal and pyloric motility was monitored in vivo by a sleeve and perfused side-hole manometric assembly and by antral and duodenal serosal strain gauges. Close intra-arterial injection to the pylorus of dynorphin-(1-13) (Dyn) for kappa-receptors, [D-Pen2,5]enkephalin (DPen2,5-Enk) for delta-receptors, and [N-Me-Phe3-D-Pro4]morphiceptin (PL017) and [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAGO) for mu-receptors showed no excitatory effect in the pylorus. When pyloric motor activity was increased by duodenal field stimulation 3-5 cm aboaad from the pylorus, Dyn greater than DPen2,5-Enk greater than DAGO produced a dose-dependent inhibition of the pyloric motor activity. Naloxone (200 micrograms/kg iv and 20 micrograms ia) had no effect on the pyloric excitation due to duodenal field stimulation, but it reduced the inhibitory response of intra-arterially injected opioids. In addition, opioid binding ([3H]diprenorphine) in microsomal and mitochondrial fractions from the inner circular muscle ring of the pylorus showed a distribution similar to the neuronal marker [3H]saxitoxin but no correlation to the plasma membrane marker 5'-nucleotidase. These results suggest the existence of inhibitory opioid receptors (kappa- and delta-receptors) on excitatory neurons in the intestinal neuronal pathway, which activates the canine pylorus.

Regulation of neural responses in the canine pyloric sphincter by opioids

“…This region has been shown to contain a very high density of opioid-containing neurones in several species (Edin et al, 1980;Ferri et al, 1987;Allescher et al, 1988). We found that exogenous opioids reduced the amplitude of excitatory and inhibitory junction potentials.…”

“…Emptying of solid meals was significantly slowed by the enkephalin analogue DAMME (D-Ala2, MePhe4, Met(O-Ol-enkephalin; FK33-824) (Sullivan et al, 1981), but others reported that naloxone did not affect gastric emptying (Feldman et al, 1980). Allescher et al (1988) found that exogenous opioid agonists inhibited motor activity of the canine pylorus in vivo. Naloxone antagonized these effects, demonstrating the presence of functional opioid receptors in the canine pylorus.…”

“…Both excitatory and inhibitory junction potentials can be 17" Macmillan Press Ltd, 1993 elicited in the circular muscle of the canine pylorus (Vogalis & Sanders, 1990), and a high density of enkephalinergic nerve fibres exists in the muscularis externa of the dog (Allescher et al, 1988), as well as in man (Ferri et al, 1987) and cat (Edin et al, 1980). Opioids may have a physiological role in pyloric function since opioid agonists have been shown to delay gastric emptying (Sullivan et al, 1981).…”

The influence of opioids on gastric function: experimental and clinical studies

“…MORs are widely distributed on cell membranes in the body and are present in the central nervous system (45)(46)(47) including at the spinal level (48), on peripheral nerves (49), and in the gastrointestinal tract (41,(50)(51)(52).…”

“…Opioids affect a variety of functions including motility (41,51,52,(61)(62)(63)(64)(65) and secretion (57), and both μ-and κ-receptors are involved (40).…”