Suppressive effect of met-enkephalin on bone marrow cell proliferation in vitro shows circadian pattern and depends on the presence of adherent accessory cells

The cellularity of femoral bone marrow and the content of the granulocyte-macrophage colony forming cells (GM-CFC) were followed in mice between 0600 h and 1800 h. The cellularity increased at the beginning of the light period, and the GM-CFC content at the end. Opioid pentapeptide methionine-enkephalin reduced the GM colony forming ability of the bone marrow cell suspensions in proportion to the GM-CFC content. Removal of the accessory cells reversed the enkephalin sensitivity pattern of the GM-CFC. The circadian variations have been ascribed to a neuroendocrine regulatory network involving the opioid peptides and affecting the bone marrow accessory cells. The work draws attention to the circadian activity pattern of hemoregulatory oligopeptides applicable as adjuvants to antineoplastic chemotherapy.