This study was designed to determine whether cells of the oligodendroglial lineage express neuroligand receptors linked to Ca2+ mobilization. Intracellular Ca'+ levels were monitored with a video-based imaging system and cells were characterized with immunocytochemical markers. 0-2A progenitor cells (A2B5+/GFAE-) and mature oligodendroglia (GC +/MBP+ ) responded to norepinephrine, glutamate, ATP, and histamine with increased intracellular Ca2+ levels. As 0-2A progenitor cells differentiated into mature oligodendroglia, there was an increase in the percentage of cells that responded to ATP and histamine with an increase in intracellular Ca2+ levels. Both 0-2A progenitor cells and mature oligodendroglia were pharmacologically heterogeneous with respect to their ability to respond to neuroligands with an increase in intracellular Ca". Treatment with bradykinin, carbachol, and substance P also increased intracellular Ca'+ levels in 0-2A progenitor cells and mature oligodendroglia. Whereas the percentage of cells that responded to bradykinin and substance P increased with differentiation of 0-2A progenitor cells into mature oligodendroglia, the trend was reversed with respect to the percentage of cells responding to carbachol. These results suggest that cells of the oligodendroglial lineage exhibit neuroligand receptors linked to Ca2+ mobilization and that the ability of these cells to respond to neuroligands is developmentally regulated. Q 1993 Why-Liss, Inc.