Inhibition of the expression of ornithine decarboxylase by some K-opioidergic receptor ligands in difluoromethylornithine-resistant L1210 cells

摘要

In difluoromethylornithine resistant L1210 cells stimulated to growth from quiescence, the selective K-opioidergic agonist trans-(±)-3,4-dichloro-A'-[2-(l-pyrrolidinyI)cyclohexyl]benzeneacetamide (U-50488H) caused a dose dependent inhibition of the induction of ODC activity, with a half-maximal effect at about 1 fj,M. U-50488H also provoked reduction of ODC mRNA level and increase of ODC turnover, as well as inhibition of cell growth. U-69593, another K-selective agonist, was only slightly effective. The action of U-50488H on ODC induction was not blocked by naloxone, /3-chlornaltrexamine or by the K-selective opioid antagonists Mrl452 and nor-bi-naltorphimine (nBNI). Actually Mrl452 and nBNI exerted some inhibitory effect. Furthermore, the separated enantiomers ( + ) and ( -) of U-50488H were similarly effective. The (-)cw-(15,2^)-U50488 stereoisomer, exhibiting low affinity for K and high affinity for a receptors and carbetapentane, another a ligand, also inhibited ODC induction, although less effectively than U-50488H. None of several other opioid ligands tested had significant effects on ODC induction. In conclusion, the inhibition of ODC expression by U-50488H does not involve classical, enantiospecific opioid receptors; rather, these results suggest the involvement of a distinct site of action linked to inhibition of lymphoid cell proliferation.