The inhibition of ornithine decarboxylase activity in developing rat tissues by central nervous system beta-endorphin is mediated by mu-opioid receptors, but not by delta- or epsilon-opioid receptors.
Our laboratory has previously shown that intracerebroventricular (i.c.v.) administration of beta-endorphin suppresses brain and liver ornithine decarboxylase activity (ODC; a growth regulatory enzyme) in preweanling rats. This investigation examined, in 6-day-old rats, the relative participation of brain mu-, delta- and epsilon-opioid receptors in beta-endorphin's ODC effects, by comparing tissue ODC responses to beta-endorphin given alone i.c.v. and in the presence of D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP; mu-opioid receptor antagonist), N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI-174,864; delta-opioid receptor antagonist) or beta-endorphin-(1-27) (epsilon-opioid receptor antagonist). Administration of 0.5 microgram of beta-endorphin alone significantly decreased brain and liver ODC activity 4 h after injection, and the effect was completely blocked by coinjection of CTOP (0.075 micrograms) but not by ICI-174,864 (0.75 or 3.75 micrograms) or beta-endorphin-(1-27) (3.75 or 7.5 micrograms). The blockade of endogenous opioid:opioid receptor interactions by either CTOP (at doses > 0.075 microgram) or ICI-174,864 alone was accompanied by increased levels of basal ODC activity. The results obtained demonstrate that i.c.v. beta-endorphin downregulates ODC expression in central as well as in peripheral tissues by interacting with brain mu-opioid receptors, but not with delta- or epsilon-opioid receptors or mu/delta-opioid receptor complexes. Also, they indicate that endogenous opioid systems have a tonic inhibitory influence on ODC activity which is mediated, at least in part, by mu- and delta-opioid receptors.
Department of Pharmacology, Duke University, Durham, NC 27710, USA.
J V
JV
Bartolome
K J
KJ
Chang
M B
MB
Bartolome
D000595:Amino Acid Sequence; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D005260:Female; D007276:Injections, Intraventricular; D008099:Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D009292:Narcotic Antagonists; D065108:Ornithine Decarboxylase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors*; D001615:beta-Endorphin / Q000008:administration & dosage / Q000494:pharmacology*
D009292:Narcotic Antagonists; D065108:Ornithine Decarboxylase Inhibitors; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C043460:epsilon receptor; D001615:beta-Endorphin