EFFECT OF OPIOID-PEPTIDES ON CIRCULAR MUSCLE OF CANINE DUODENUM

1. The effects of opioid peptides on inhibitory transmission in the circular muscle layer of canine duodenum were investigated in vitro using simultaneous mechanical and intracellular electrical recording techniques. 2. Exogenously added [Met5]enkephalin, [Leu5]enkaphalin and dynorphin (1-13) decreased the amplitude of non-adrenergic, non-cholinergic inhibitory junction potentials (IJPs) evoked by transmural nerve stimulation. 3. A selective delta-receptor agonist, DPDPE ([D-Pen2, D-Pen5]enkephalin), and a selective mu-receptor agonist, PL017 (Try-Pro-NMePhe-D-Pro-NH2), decreased the amplitude of IJPs whereas a selective kappa-receptor agonist, U-50,488H ([trans-3,4-dichloro-N-methyl-N-(2-91-pyrolidinly)-cyclohexyl]-bezeneacetamide methanesul-phonate), in large doses (1-mu-M) produced only a small reduction. 4. A selective delta-receptor antagonist. ICI-174.864, blocked the effect of DPDPE but not that of PL017 suggesting the presence of distinct delta- and mu-opioid receptors on inhibitory motor nerves. 5. Exogenously added dynorphin (1-13) decreased the amplitude of IJPs. delta-Opioid receptors appeared to be involved because ICI-174,864, a selective delta-antagonist, blocked the inhibitory effect of exogenously added dynorphin (1-13). 6. The inhibitory effect of the opiod peptides was still observed in preparations of circular muscle devoid of myenteric and submucosal plexuses, indicating that the site of action was on inhibitory motor nerve fibres located within the circular muscle layer and not on neuronal cell bodies in the enteric plexuses. 7. It was concluded that in the canine small intestine, opioid peptides could modulate release of inhibitory transmitter(s) at or near nerve of inhibitory motor nerves innervating circular muscle cells.