Effects of central administration of beta-endorphin on brain and liver DNA synthesis in preweanling rats.
We have previously shown that central administration of beta-endorphin results in a reduction of ornithine decarboxylase activity. Ornithine decarboxylase catalyses the rate-limiting step in the biosynthesis of the polyamines putrescine, spermidine and spermine, thought to modulate nucleic acid synthesis. The present study examines the effects of intracisternal injection of beta-endorphin on brain and liver DNA synthesis in preweanling rats. In six-day-old rats, beta-endorphin (0.75 micrograms/g brain wt) produced approximately a 70% inhibition in brain and liver DNA synthesis 1 h after injection, and values were still subnormal in both tissues 10 h later. Subcutaneous administration of beta-endorphin did not alter liver DNA synthesis. Thus, it is most likely that the suppressed liver DNA synthesis observed in animals given beta-endorphin intracisternally is mediated by central mechanisms. Co-administration of naloxone plus beta-endorphin intracisternally prevented the response, indicating an opioid receptor-mediated phenomenon. Naloxone alone caused small but significant increases in brain and liver DNA synthesis, suggesting a tonic influence on tissue DNA by endogenous opioids in the CNS. Acute inhibition of ornithine decarboxylase activity by alpha-difluoromethylornithine did not alter DNA synthesis, indicating that the decreases in DNA synthesis induced by beta-endorphin are unrelated to the ornithine decarboxylase/polyamine system. The effect appears to be restricted to early development as no significant changes in DNA synthesis were obtained in 20-day-old animals. The results from these studies indicate that CNS beta-endorphin has the ability to influence DNA synthesis in central as well as in peripheral tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
Bartolome
J V
JV
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Bartolome
M B
MB
Lorber
B A
BA
Dileo
S J
SJ
Schanberg
S M
SM
D000818:Animals; D000833:Animals, Suckling; D001921:Brain / Q000378:metabolism* / Q000502:physiology*; D004247:DNA / Q000096:biosynthesis*; D007267:Injections; D008099:Liver / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D001615:beta-Endorphin / Q000494:pharmacology*
D009270:Naloxone; D001615:beta-Endorphin; D004247:DNA