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Oligopeptide fragments of the enkephalin molecule interfere with hematopoietic cell colony formation

The common acute lymphoid leukemia antigen (CALLA, CD 10) is one of the surface markers of lympho-hematopoietic cells. This neutral metallopeptidase (NEP 24.11) cleaves varius peptides including enkephalins (hence is name enkephalinase). In our hands, penatapeptide methionin-enkephalin Tyr-Gly-Gly-Phe-Met suppressed granulocyte-machrophage (GM) colony growth of mouse bone marow cells in vitro. Continuing that work, we wanted to see whether oligopeptide fragments of methionin enkephalin interfere with the GM-colony formation in vitro. Clonal culture of bone marrow cells in soft agar was applied as the experimental system. Here we describe the effect synthehetic oligopeptides representing NH2-terminal of the enkephalin molecule (dipeptide Tyr-Gly, tripeptide Tyr-Gly-Gly and tetrapeptide Tyr-Gly-Gly-Phe), the COOH-terminal (dipeptide Phe-Met) or the intermediate portion (dipeptide Gly-Gly). These agents were assayed in complete bone marrow cell population, and in monocyte depleted population to see whether the substances affected the progenitor cells by a direct action or via the accessory cells (monocytes). Naloxone, agent that bloks opioid receptors was used to examine whether the effect of enkephaline degradation product on bone marrow cells was mediated by these receptors. Dipeptide Tyr-Gly and tripeptideTyr-Gly-Gly having the NH2-terminal aminoacid tyrosine inhibited GM colony formation in clonal culture of mouse bone marrow. Oligopeptide fragment representing the intermediate (dipeptide Gly-Gly) or the COOH-portion of the enkephaline molecule (dipeptide Phe-Met) were innefective. The suppressive action of dipeptide Tyr-Gly and tripeptide Tyr-Gly-Gly on the proliferation of mouse GM-progenitors depended on the presence of the accessory cells in the bone marow cell population. Naloxone, an opioid receptor bloking agent, did not abolish the suppressive effect of the oligopeptide enkephalin fragments dipeptide Tyr-Gly and tripeptide Tyr-Gly-Gly. That data suggest that oligopeptide fragments of methionin-enkephalin containing the NH2-terminal aminoacid tyrosine affect mouse hematopoietic cells like parent molecule of methionin-enkephalin, but probably by nonopioid mechanisms of action and that suppressive effect of these agents depended on the presence of the accessory cells.

bone marrow cells; methionine enkephalin; oligopeptide enkephalin fragments; CFU-GM; naloxone

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