EVIDENCE FOR LACK OF MODULATION OF MU-OPIOID AGONIST ACTION BY DELTA-OPIOID AGONISTS IN THE MOUSE VAS-DEFERENS AND GUINEA-PIG ILEUM

1 There is evidence from in vivo studies for an interaction of mu- and delta-opioid ligands. In the present work this concept has been investigated using the mouse vas deferens and guinea-pig ileum myenteric plexus-longitudinal preparations. 2 In field stimulated vasa deferentia of the mouse, co-administration of sub-effective concentrations of the delta-opioid agonist [D-Pen(2),D-Pen(5)]enkephalin (DPDPE) and [Met(5)]- or [Leu(5)]enkephalin had no effect on the dose-response curves of the mu-agonists [D-Ala(2),MePhe(4),Gly-ol(5)]enkephalin (DAMGO) and morphine. Similarly, the delta-opioid agonists did not alter the potency of morphine and DAMGO when added at different times prior to the mu-opioid agonists, or when EC(50) cconcentrations of delta-opioid ligands were co-administered. Compounds with preferred activity for the putative delta(1)-(DPDPE) or delta(2)- ([D-Ala(2),Glu(4)]deltorphin II (Delt II)) opioid receptors were ineffective in this respect. 3 The guinea-pig ileum contains g-opioid receptors. No function of these receptors in mediating blockage of field-stimulated contractions was observed with ligands having affinity for the putative delta(1) or delta(2) subtypes nor were the agonists able to modulate responses to mu-opioid ligands in this tissue. 4 The results demonstrate that modulation of mu-opioid agonists by delta-opioid agonists does not occur in the isolated peripheral tissues examined. Thus the findings do not support the concept of a functional coupling of opioid receptors, though the results may be explained by differences between opioid systems in the brain and peripheral tissues examined.