The opioid peptide methionine (Met)-enkephalin and the opioid-receptor blocking agent naloxone were added to unseparated or to progenitor-enriched cell suspensions of mouse bone marrow before assay in clonal cultures. Bone marrow samples harvested at 18:00 hours produced more granulocyte-macrophage (GM) colonies than the 06:00 hour samples, and were more sensitive to the proliferation inhibition by both agents. Additive inhibitory effects of naloxone with the enkephalin were occasionally seen. Thus, in this experimental system, naloxone could behave as an opioid agonist. However, there were examples of naloxone diminishing (blocking) the suppressive effect of the enkephalin, as a true opioid antagonist. Significant naloxone/enkephalin interactions occurred in opioid-sensitive (18.00 h) samples of unseparated bone marrow. The interactions were virtually absent in progenitor cell-enriched populations, indicating a significant role of accessory cells in opioidergic regulation of hematopoietic progenitors.
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