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 that the delta-opioid agonist DTLET inhibits the release of the Gonadotropin-Releasing Hormone (GnRH) from hypothalamic fragments containing the arcuate nucleus and the median eminence. This effect is receptor mediated and eicosanoid dependent (Gerozissis et al., 1993). 2. In the present study we report that the delta-opioid antagonists with negative intrinsic activity, Diallyl-G and ICI 174864, applied under the same experimental conditions (30 min static incubations at 37 degrees C, in a potassium rich milieu), in the absence of the agonist DTLET, also exert 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 opioid antagonist, naloxone is without effect in the absence of DTLET. However, naloxone acts as an antagonist on the Diallyl-G-induced inhibition of GnRH release. 4. Diallyl-G also inhibits the release of prostaglandin E2 (PGE2). In the presence of indomethacin or nordihydroguaiaretic 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 PGE2 but not leukotrienes participate in the agonist-independent effects of Diallyl-G on GnRH release. 5. Therefore these results support the hypothesis that delta-opioid antagonists with negative intrinsic activity exert agonist-independent biological responses similar to those of the agonists.
Dragatsis
I
I
Institute of Biology, National Centre for Scientific Research, Attiki, Greece.
Zioudrou
C
C
Gerozissis
K
K
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D015777:Eicosanoids / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015289:Leukotrienes / Q000096:biosynthesis; D008297:Male; D008473:Median Eminence / Q000378:metabolism; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors*
D015777:Eicosanoids; D015289:Leukotrienes; D009292:Narcotic Antagonists; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; C082083:diallyl G; D016718:Arachidonic Acid; D007987:Gonadotropin-Releasing Hormone; D009270:Naloxone; C037653:deltakephalin; D015232:Dinoprostone