SPECIFIC DELTA-OPIOID ANTAGONISTS EXERT AN AGONIST-INDEPENDENT INHIBITORY EFFECT, SIMILAR TO THE AGONIST, ON THE RELEASE OF GNRH IN-VITRO

1. In in vitro studies with adult male rats we have recently shown tha t the delta-opioid agonist DTLET inhibits the release of the Gonadotro pin-Releasing Hormone (GnRH) from hypothalamic fragments containing th e arcuate nucleus and the median eminence. This effect is receptor med iated and eicosanoid dependent (Gerozissis et al., 1993). 2. In the pr esent study we report that the delta-opioid antagonists with negative intrinsic activity, Diallyl-G and ICI 174864, applied under the same e xperimental conditions (30 min static incubations at 37 degrees C, in a potassium rich milieu), in the absence of the agonist DTLET, also ex ert a similar to the agonist inhibitory effect on the release of GnRH. 3. The dose-dependent inhibitory effect of Diallyl-G on GnRH release is reversed by increasing concentrations of DTLET. The mu and delta op ioid antagonist, naloxone is without effect in the absence of DTLET. H owever, naloxone acts as an antagonist on the Diallyl-G-induced inhibi tion of GnRH release. 4. Diallyl-G also inhibits the release of prosta glandin E(2) (PGE(2)), In the presence of indomethacin or nordihydrogu aiaretic acid, Diallyl-G is ineffective to further inhibit the release of GnRH. These latter observations taken together with the results of eicosanoid estimation suggest that PGE(2) but not leukotrienes partic ipate in the agonist-independent effects of Diallyl-G on GnRH release. 5. Therefore these results support the hypothesis that delta-opioid a ntagonists with negative intrinsic activity exert agonist-independent biological responses similar to those of the agonists.