Effects of propofol on P2X7 receptors and the secretion of tumor necrosis factor-α in cultured astrocytes

• DOI: 10.1007/s10238-011-0139-4
• Publication Date: 2011-05-23T11:59:18Z
• Authors: Jia Liu; Xiao-Fei Gao; Wen Ni; Jin-Bao Li
• Keywords: 0301 basic medicine; Patch-Clamp Techniques; Time Factors; Tumor Necrosis Factor-alpha; Enzyme-Linked Immunosorbent Assay; Electrophysiological Phenomena; Rats; Purinergic P2X Receptor Agonists; 03 medical and health sciences; Adenosine Triphosphate; Neuroprotective Agents; Astrocytes; Rosaniline Dyes; Animals; Receptors, Purinergic P2X7; Neuroglia; Propofol; Cells, Cultured

Upon CNS injury, adenosine-5'-triphosphate is released and acts on P2X7 receptors, which might influence many cytokines secretion from glial cells and, in turn, affects the survival of neurons. Propofol, an intravenous anesthetic, has been shown to provide neuroprotective effect. However, the effect of propofol on astrocyte-associated processes remains to be clarified. In this study, we investigated the effects of propofol on P2X7 activity in astrocytes and tumor necrosis factor-α (TNF-α) secretion from these cells and thereby to infer the possible role(s) of glial P2X7 receptors in propofol neural protective effects. Whole-cell patch clamp results showed that in clinically relevant concentrations (3.3, 10 or 33 μM), propofol increased the P2X7 current amplitudes significantly and propofol in 10 μM extended the inactivation times of P2X7 receptors. Enzyme-linked immunosorbent assay showed that propofol increased the secretion of TNF-α from astrocytes in high concentration (300 μM), while inhibited in clinically relevant concentration (10 μM). Both of these effects were not influenced by Brilliant blue G. These results suggest that in clinically relevant concentrations, propofol increases the activity of P2X7 receptors in activated astrocytes, but this does not contribute to the downregulation of the secretion of TNF-α.