Inhibition of oestradiol-induced DNA synthesis by opioid peptides in the rat uterus

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.