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 17 beta-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 (approximately 50%) 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 approximately 0.26 and approximately 0.45 microgram/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 17 beta-oestradiol priming no significant effect of [D-Met2,Pro5]-enkephalinamide or naloxone on [3H]TdR incorporation was found.
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Hungarian Academy of Sciences, Institute of Physiology, Pécs.
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D000818:Animals; D004247:DNA / Q000096:biosynthesis*; D004723:Endorphins / Q000494:pharmacology*; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D010052:Ovariectomy; D051381:Rats; D011919:Rats, Inbred Strains; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D004723:Endorphins; D004965:Estrogen Antagonists; D009270:Naloxone; D004958:Estradiol; D004744:Enkephalin, Methionine; C021717:enkephalin, Met(2)-ProNH2(5)-; D004247:DNA