Thromboxane A(2) receptor-mediated signal transduction in rabbit aortic smooth muscle cells

1. 9,11-Epithio-11,12-methenothromboxane A(2) (STA(2)), a stable analogue of thromboxane A(2) (TXA(2)), contracted rabbit aortic smooth muscles (RASM) and accumulated [H-3]inositol phosphates in cultured RASM cells. The contraction and phosphoinositide hydrolysis were competitively inhibited by TXA(2) receptor antagonists, including ONO NT-126, S-145, S429548, KW3635, GR32191B and ONO3708. 2. STA(2) inhibited [H-3]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 STA,induced inhibition of [3H]ONO NT-126 binding. 3. The time course analysis revealed that STA(2) rapidly decreased inositol phosphate level and thereafter increased. Pertussis toxin did not attenuate but rather increased STA(2)-induced phosphoinositide hydrolysis. 4. TXA(2) receptor stimulation results in at least two signaling pathways in RASM cells: stimulation and inhibition of phosphoinositide hydrolysis.