Abstract
The f chemokine receptor CXCR4 is used as the major coreceptor for the cell entry of T-cell-tropic human immunodeficiency virus-1 (HIV-1) isolates. Activation of this coreceptor by its natural ligand SDF1 f is associated with an intracellular Ca 2+ increase. Because the HIV-1 glycoprotein 120 (gp120) is shedded from the surface of HIV-1-infected cells and is regarded as an injurious molecule in the pathogenesis of HIV-1-associated encephalopathy (HIVE), we investigated the effects of gp120 on the intracellular Ca 2+ regulation of astrocytes and neurons. After 5 days in vitro (DIV), SDF1 f (50 nM) elicited a pertussis toxin-sensitive intracellular Ca 2+ increase due to Ca 2+ release from internal stores that was reduced by a blocking monoclonal antibody against the CXCR4 receptor in astrocytes and neurons. Parallel with the development of the SDF1 f response, cells became sensitive to direct application of gp120 (1.25 w g/ml), which, similarly to SDF1 f , elicited a transient intracellular Ca 2+ increase. However, short-term incubation with gp120 for 60 to 120 min induced a reduction of glutamate- or ATP-evoked intracellular Ca 2+ responses only in astrocytes and not in neurons, although functional CXCR4 receptors were expressed in both cell types. Therefore, our data strongly suggest that the CXCR4 receptor-mediated intracellular signaling pathway of gp120 differs in astrocytes and neurons.