Publications (2)10.31 Total impact
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ABSTRACT: This study was designed to determine whether cells of the oligodendroglial lineage express neuroligand receptors linked to Ca2+ mobilization. Intracellular Ca2+ levels were monitored with a video-based imaging system and cells were characterized with immunocytochemical markers. O-2A progenitor cells (A2B5+/GFAP-) and mature oligodendroglia (GC+/MBP+) responded to norepinephrine, glutamate, ATP, and histamine with increased intracellular Ca2+ levels. As O-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 O-2A progenitor cells and mature oligodendroglia were pharmacologically heterogeneous with respect to their ability to respond to neuroligands with an increase in intracellular Ca2+. Treatment with bradykinin, carbachol, and substance P also increased intracellular Ca2+ levels in O-2A progenitor cells and mature oligodendroglia. Whereas the percentage of cells that responded to bradykinin and substance P increased with differentiation of O-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.
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ABSTRACT: Cultured astroglia express purinergic receptors that initiate phosphoinositide metabolism and calcium mobilization. Experiments were conducted to characterize the purinergic receptor subtype on type 1 astroglia responsible for stimulation these second-messenger systems. Inositol phosphate (IP) accumulation and calcium mobilization were measured after stimulation with ATP or purinergic receptor subtype-selective ATP analogues. ATP (10(-5) M) increased IP accumulation severalfold. Dose-effect assays monitoring astroglial IP accumulation revealed the order of potency that defines the P2Y receptor: 2-methylthioadenosine 5'-triphosphate greater than ATP greater than alpha beta-methyleneadenosine 5'-triphosphate greater than beta gamma-methyleneadenosine 5'-triphosphate. The influence of ATP on intracellular calcium levels in individual type 1 astroglia was examined using the calcium indicator dye, fura-2. Dose-effect experiments indicated that ATP was equally potent for generating inositol phosphates and increasing cellular calcium. The most prevalent response (87% of total responses) to ATP consisted of a rapid increase in calcium to a peak level that was approximately five times greater than the prestimulation level. This peak was followed by a decline to a plateau level that was significantly above baseline. This plateau phase of the calcium increase was maintained for at least 5 min in the presence of ATP and was dependent on external calcium. Many (23%) astroglia exhibited spontaneous calcium oscillations whose frequency and magnitude increased after the addition of 10(-5) M ATP. Immunocytochemical staining indicated that the responses occurred in glial fibrillary acidic protein positive cells. We conclude that type 1 astroglia express the P2Y purinergic receptor which regulates IP production and calcium mobilization.
University of North Carolina at Chapel Hill
North Carolina, United States
- Department of Pharmacology