Thromboxane A2 receptor-mediated signal transduction in rabbit aortic smooth muscle cells.

1. 9,11-Epithio-11,12-methenothromboxane A2 (STA2), a stable analogue of thromboxane A2 (TXA2), contracted rabbit aortic smooth muscles (RASM) and accumulated [3H]inositol phosphates in cultured RASM cells. The contraction and phosphoinositide hydrolysis were competitively inhibited by TXA2 receptor antagonists, including ONO NT-126, S-145, SQ29548, KW3635, GR32191B and ONO3708. 2. STA2 inhibited [3H]ONO NT-126 binding in a concentration-dependent manner in membranes derived from cultured aortic smooth muscle cells, but GTP gamma S, a stable GTP analogue, did not affect STA2-induced inhibition of [3H]ONO NT-126 binding. 3. The time course analysis revealed that STA2 rapidly decreased inositol phosphate level and therefter increased. Pertussis toxin did not attenuate but rather increased STA2-induced phosphoinositide hydrolysis. 4. TXA2 receptor stimulation results in at least two signaling pathways in RASM cells: stimulation and inhibition of phosphoinositide hydrolysis.