The inhibition of ornithine decarboxylase activity in developing rat tissues by central nervous system β-endorphin is mediated by μ-opioid receptors, but not by δ- or ϵ-opioid receptors

Abstract

Our laboratory has previously shown that intracerebroventricular (i.c.v.) administration of β-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 μ-, δ- and ϵ-opioid receptors in β-endorphin's ODC effects, by comparing tissue ODC responses to β-endorphin given alone i.c.v. and in the presence of d-Phe-Cys-Tyr- d-Trp-Orn-Thr-Pen-Thr-NH 2 (CTOP; μ-opioid receptor antagonist), N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI-174,864; δ-opioid receptor antagonist) or β-endorphin-(1–27) (ϵ-opioid receptor antagonist). Administration of 0.5 μg of β-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 μg) but not by ICI-174,864 (0.75 or 3.75 μg) or β-endorphin-(1–27) (3.75 or 7.5 μg). The blockade of endogenous opioid:opioid receptor interactions by either CTOP (at doses > 0.075 μg) or ICI-174,864 alone was accompanied by increased levels of basal ODC activity. The results obtained demonstrate that i.c.v. β-endorphin downregulates ODC expression in central as well as in peripheral tissues by interacting with brain μ-opioid receptors, but not with δ- or ϵ-opioid receptors or μ/δ-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 μ- and δ-opioid receptors.