Role of the spinal cord in intracisternal beta-endorphin-evoked suppression of liver DNA synthesis in 10-day-old rats.
Previously, we have shown that intracisternal (i.c.) administration of beta-endorphin (an opioid peptide naturally occurring in the brain) to preweanling rats markedly decreases DNA synthesis (an index of cell proliferation) in both brain and liver. This observation is consistent with our hypothesis that endogenous CNS beta-endorphin plays an important role in controlling postnatal growth. The current research specifically undertook to investigate, in 10-day-old rats, whether or not i.c. beta-endorphin-evoked suppression of liver DNA synthesis is actually mediated by spinal opioid receptors and/or by descending endorphinergic pathways. In contrast to the i.c. route of administration, beta-endorphin given directly into the spinal subarachnoid space via intrathecal (i.t.) injection did not alter liver DNA synthesis, yet was able to evoke profound antinociceptive responses. This demonstrates that intracisternally applied beta-endorphin exerts its effect on liver DNA by acting at supraspinal sites, and not by directly stimulating spinal opioid receptors after diffusion from its intracerebral site of injection. As it is possible that beta-endorphin's supraspinal actions may activate a descending inhibitory endorphinergic pathway to reduce DNA synthesis, we conducted studies in rat pups administered naloxone intrathecally. Naloxone i.t. was completely ineffective in preventing beta-endorphin i.c. from inhibiting liver DNA synthesis. On the other hand, i.t. coinjection of naloxone plus beta-endorphin was able to block the analgesic response, while their i.c. coinjection reversed the DNA effect. The results from these studies indicate that opioid systems within the spinal cord do not play a major role in mediating CNS beta-endorphins regulation of DNA synthesis in peripheral tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Duke University, Durham, NC 27710.
J V
JV
Bartolome
M B
MB
Bartolome
D000818:Animals; D002946:Cisterna Magna; D004247:DNA / Q000096:biosynthesis*; D004058:Diffusion; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000502:physiology*; D013346:Subarachnoid Space; D001615:beta-Endorphin / Q000008:administration & dosage*
D001615:beta-Endorphin; D004247:DNA