Objective: Opioid receptor expression and function traditionally have been studied in neuronal cells and recently in mature lymphoid cells; however, little is known about their possible functions in hematopoietic stem cells (CD34(+) cells). We studied the expression of the mu receptor on CD34(+) cells and assessed the signal transduction cascade it induces.
Materials and methods: Mu-receptor expression on cord blood (CB) and peripheral blood (PB) CD34(+) cells was studied by microarrays, immunostaining, and fluorescence-activated cell sorting analysis. Signal transduction by the mu receptor was studied through Western blots and kinase assay of enkephalin-activated CB CD34(+) cells. Apoptotic, differentiation, and proliferation responses following mu-receptor activatioSn were studied by annexin V assay and inverted microscopy.
Results: A prominent difference in gene expression, in favor of CB compared to PB CD34(+) cells, was observed in the mu-receptor gene. This receptor was mainly expressed on the CB CD34(+)CD38(-) subpopulation. A MAP kinase signal transduction cascade was shown to be induced through activation of this receptor by enkephalin or morphine.
Conclusions: We showed for the first time that the mu receptor is expressed on immature CB stem cells and that its activation by enkephalin or morphine induces a MAP kinase signal transduction cascade. Because the MAP kinase cascade is known to elicit proliferation and differentiation responses, these findings suggest a possible role of endogenous enkephalins in hematopoietic stem cell proliferation and differentiation and may lead to therapeutic applications of opiates in CB stem cell expansion and neuronal differentiation.