Inhibitory effects of ONO-3708 and S-145 on shape change and aggregation of rabbit platelets induced by STA2.
OBJECTIVE
To study the mode of inhibition of ONO-3708 and S-145, 2 antagonists of thromboxane A2 (TXA2) receptors, against the rabbit platelet shape change and aggregation induced by stable analogue of TXA2 (STA2).


METHODS
The platelet shape change and aggregation were quantified by the light transmission through platelet-rich plasma (PRP) and the intracellular calcium concentration ([Ca2+]i) was measured by fluorescence and imaging.


RESULTS
(1) In PRP, STA2 (3 mumol.L-1)-induced aggregation was inhibited by egtazic acid 3 mmol.L-1, ONO-3708 300 mumol.L-1, and S-145 1 mumol.L-1 (P < 0.01), but not by indometacin (Ind) 3 mumol.L-1. The shape change induced by STA2 was inhibited only by S-145 in a concentration-dependent manner. S-145 1 and 3 mumol.L-1 were required to inhibit the shape change and aggregation. (2) The inhibitory effect of S-145, but not ONO-3708, was increased along with the prolongation of preincubation. (3) ONO-3708 lost the inhibitory effect on STA2-induced aggregation after washing, while the inhibitory effect of S-145 was enhanced by prolongation of preincubation and remained after washing. (4) STA2 3 mumol.L-1-induced [Ca2+]i mobilization was unaffected by Ind, partially reduced by ONO-3708 and egtazic acid 3 mmol.L-1 (P < 0.01), but completely inhibited by S-145 (P < 0.01).


CONCLUSIONS
S-145 and ONO-3708 were bound to a different site of the TXA2 receptor.
Li
B Y
BY
Department of Pharmacology, Harbin Medical University, China.
Qiao
G F
GF
Sun
J P
JP
Gao
Y R
YR
Li
W H
WH
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011817:Rabbits; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology
D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D010975:Platelet Aggregation Inhibitors; D011448:Prostaglandin Antagonists; D017482:Receptors, Thromboxane; C056566:S 145; D013928:Thromboxane A2; C037866:STA 2; C049855:ONO 3708