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-OPIOID 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 mu g 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 mu g) but not by ICI-174,864 (0.75 or 3.75 mu g) or beta-endorphin-(1-27) (3.75 or 7.5 mu g). The blockade of endogenous opioid:opioid receptor interactions by either CTOP (at doses > 0.075 mu g) 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.