Thromboxane A2 receptor-mediated G12/13-dependent glial morphological change

Glial cells express thromboxane A2 receptor, but its physiological role remains unknown. The present study was performed to examine thromboxane A2 receptor-mediated morphological change in 1321N1 human astrocytoma cells. Thromboxane A2 receptor agonists U46619 and STA2 caused a rapid morphological change to spindle shape from stellate form of the cells pretreated with dibutyryl cyclic AMP, but neither carbachol nor histamine caused the change, suggesting that Gq pathway may not mainly contribute to the change. Rho kinase inhibitor Y-27632 inhibited U46619-induced morphological change, and U46619 increased the GTP-bound form of RhoA accompanied with actin stress fiber formation. These responses were reduced by expression of p115-RGS that inhibits G12/13 signaling pathway. U46619 also caused the phosphorylation of extracellular signal-regulated kinase (ERK) and [3H]thymidine incorporation mainly through G12/13-Rho pathway. These results suggest that stimulation of thromboxane A2 receptor causes the morphological change with proliferation mainly through G12/13 activation in glial cells.