RESEARCH OF THROMBOXANE A_2 RECEPTOR SUBCLASS AND THEIR SIGNAL TRANSDUCTION

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We found for the first time that 1321N1 human astrocytoma cells express thromboxane A_2 (TXA_2) receptor in 1989. The stimulation of TXA_2 receptor resulted in Ca^<2+> -mobilization mediated via pertussis toxin-insensitive, G protein, Gq, phospholipase C-beta (PLC- beta) and inositol 1,4,5-trisphosphate (TP3) accumulation. Analysis of TXA_2 receptor in platelets and vascular smooth muscles revealed that TXA_2 receptor stimulation caused an activation of a signaling pathway other than Gq/PLC-beta/IP_3/Ca^<2+> pathway. The present study was undertaken to clarify the TXA_2-receptor-mediated signaling pathway other than Gq/PLC-beta/IP_3/Ca^<2+> pathway. In human astrocytoma cells, TXA_2 receptor was coupled to a new pertussis toxin-insensitive G protein G_<12>. The stimulation of TXA_2 receptor resulted in activation of mitogen-activated protein kinase (MAPK) mediated via phosphatidylcholine-specific phospholipase C (PC-PLC) and protein kinase C.The human astrocytoma cells also expressed two alternative splicing products of TXA_2 receptor, placental and endothelial types. In the differentiated astrocytoma cells by dibutyryl cyclic AMP, TXA_2 receptor stimulation caused a weak Ca^<2+> mobilization, but a potent activation of MAPK.These results indicate that G_<12>/PC-PLC pathway is a novel-signaling pathway of TXA_2 receptor stimulation.