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-Met², Pro⁵]enkephalinamide on the DNA synthesis in the uterus of 7, 14 and 21-day-old rat were studied. After [D-Met²,Pro⁵]enkephalinamide treatment, an age-dependent decrease in in vitro [³H]thymidine incorporation into DNA was observed in all studied age groups. In the 21-day-old age group a reduced rate of DNA synthesis was detected for 12 h after [D-Met²,Pro⁵]enkephalinamide treatment followed by the return to control values at 24 h. The rate of inhibition was more marked in the younger age groups. The effect of [D--Met²,Pro⁵]enkephalinamide treatment was completely prevented by the opioid antagonist naloxone injected 30 min prior to the agonist treatment. Naloxone itself resulted in an increase in uterine DNA synthesis. This effect was also more pronounced in younger animals. Specific [³H]naloxone binding was detected both in membrane and nuclear fractions of uterine homogenates. While no age-related changes in binding affinities were found, the number of binding sites varied characteristically during development. Our data suggest the novel involvement of opioid peptides and their receptors in the regulation of uterine development.