ROLE OF OPIOID-PEPTIDES IN THE REGULATION OF DNA-SYNTHESIS IN IMMATURE RAT UTERUS

The effects of a single dose of naloxone and of [D-Met(2),Pro(5)]enkep halinamide on the DNA synthesis in the uterus of 7, 14 and 21-day-old rat were studied. After [D-Met(2),Pro(5)]enkephalinamide treatment, an age-dependent decrease in in vitro [H-3]thymidine incorporation into DNA was observed in all studied age groups. In the 21-day-old age grou p a reduced rate of DNA synthesis was detected for 12 h after [D-Met(2 ),Pro(5)]enkephalinamide treatment followed by the return to control v alues at 24 h. The rate of inhibition was more marked in the younger a ge groups. The effect of [D-Met(2),Pro(5)]enkephalinamide treatment wa s completely prevented by the opioid antagonist naloxone injected 30 m in prior to the agonist treatment. Naloxone itself resulted in an incr ease in uterine DNA synthesis. This effect was also more pronounced in younger animals. Specific [H-3]naloxone binding was detected both in membrane and nuclear fractions of uterine homogenates. While no age-re lated changes in binding affinities were found, the number of binding sites varied characteristically during development. Our data suggest t he novel involvement of opioid peptides and their receptors in the reg ulation of uterine development.