Thromboxane A2 receptor-mediated signal transduction in glial cells

Abstract

Thromboxane A2 (TXA2) receptor subtypes and their signal transduction were examined in 1321N1 human astrocytoma cells. Placental and endothelial types of TXA2 receptor mRNA were found in astrocytoma cells by RT-PCR procedure. Using immunoaffinity column conjugated with anti-TXA2 receptor antibody, two TXA2 receptors (58 and 55 kDa) were partially purified. The partially purified TXA2 receptor fraction contained Gq/11 and G12. The incubation of the cells with dibutyryl cyclic AMP (dbcAMP) caused a differentiation of human astrocytoma cells. DbcAMP treatment resulted in the reduction of Ca2+ elevation and phosphoinositide hydrolysis induced by TXA2 receptor agonist. Whereas the responsiveness of Ca2+ signaling was weakened by dbcAMP treatment, phosphorylation of mitogen-activated protein kinase was increased in dbcAMP-treated cells. These results suggested that human astrocytoma cells express placental and endothelial TXA2 receptors. The TXA2 receptors were coupled with Gq/11 and G12. DbcAMP treatment discriminates TXA2 receptor-mediated MAPK activation from the Ca2+ signaling pathway.