Opioid drugs and peptides were investigated for their effect on uterine DNA synthesis induced by a single injection of 17β-oestradiol given to ovariectomized rats 24 h prior to decapitation. [D-Met2, Pro5]-enkephalinamide administered 12, 2 or 1 h before killing resulted in a significant (⇔ld50%) inhibition of in vitro [3H]-thymidine incorporation into DNA, while injections given 24 or 6 h before decapitation were ineffective. Non-linear regression of the dose-effect curves resulted in an ED50 of ⇔ld0.26 and ⇔ld0.45 μg/100 g b.wt. for the opioid treatments given 12 or 2 h before killing, respectively. These effects could be completely reversed by the opioid antagonist naloxone injected 30 min prior to the agonist treatment, while naloxone itself had no effect. Morphine and [D-Ala2, D-Leu5]-enkephalin administered 12 h, as well as dynorphin A fragment 1-13 given 2 h before decapitation also inhibited oestradiol-induced uterine DNA synthesis. In ovariectomized animals without 17β-oestradiol priming no significant effect of [D-Met2, Pro5]-enkephalinamide or naloxone on [3H]TdR incorporation was found.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)