Glial cells express thromboxane A(2) receptor, but its physiological role remains unknown. The present study was performed to examine thromboxane A(2) receptor-mediated morphological change in 1321N1 human astrocytoma cells. Thromboxane A(2) receptor agonists U46619 and STA(2) 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 G(q) 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 G(12)/(13) signaling pathway. U46619 also caused the phosphorylation of extracellular signal-regulated kinase (ERK) and [(3)H]thymidine incorporation mainly through G(12)/(13)-Rho pathway. These results suggest that stimulation of thromboxane A(2) receptor causes the morphological change with proliferation mainly through G(12)/(13) activation in glial cells.