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.
Yamamoto
K
K
Department of Pharmacology, Fukushima Medical College, Japan.
Ebina
S
S
Nakanishi
H
H
Nakahata
N
N
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000294:innervation; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D005260:Female; D006834:Hydrazines / Q000037:antagonists & inhibitors; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000294:innervation; D010716:Phosphatidylinositols / Q000096:biosynthesis; D011817:Rabbits; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D010716:Phosphatidylinositols; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; C037866:STA 2; C045749:SQ 29548