Selective opioid antagonist effects on opioid-induced inhibition of release of norepinephrine in guinea pig cortex

Opioid agonists with selectivity for μ, δ and κ-receptors have each been shown to inhibit the K⁺-stimulated release of [³H]norepinephrine (NE) from slices of guinea pig cortex maintained in vitro. In order to provide further evidence that each of these types of opioid receptor can regulate the release of NE in this tissue, experiments with receptor-type selective opioid antagonists have been conducted. In initial experiments, the selectivity of the antagonists for specific types of opioid receptors in the cortex of the guinea pig in an incubation medium of the same composition as that used for release studies was confirmed. The δ-receptor selective antagonist, ICI 174,864, prevented the inhibitory actions of the δ-selective agonist, [d-Pen²,d-Pen⁵]enkephalin (DPDPE), but had little effect on the inhibitory actions of the μ-selective agonist, Tyr-d-Ala-Gly-MePhe-Gly-ol (DAMGO), or the κ-selective agonist, U-50,488H. In contrast, the κ-selective antagonist, nor-binaltorphimine (nor-BNI) prevented the inhibitory actions of U-50,488H, but had little effect on the inhibitory actions of DPDPE or DAMGO. The greater potency of the partially μ -selective antagonist, naloxone, in reversing the effects of DAMGO relative to those of DPDPE or U-50.488H was confirmed. These results support the conclusion that μ- δ- and κ-opioid receptors each exert a negative regulatory effect on the stimulated release of NE in the cortex of the guinea pig.