FTIR spectral study of intramolecular hydrogen bonding in thromboxane A2 receptor agonist (U-46619), prostaglandin (PG)E2, PGD2, PGF2.alpha., prostacyclin receptor agonist (carbacyclin) and their related compounds in dilute carbon tetrachloride solution: structure-activity relationships

1994 ◽  
Vol 37 (1) ◽  
pp. 47-56 ◽  
Author(s):  
Mamoru Takasuka ◽  
Morio Kishi ◽  
Masumi Yamakawa
Keyword(s):  
Receptor Agonist ◽  
Solution Structure ◽  
Thromboxane A2 ◽  
Intramolecular Hydrogen Bonding ◽  
Thromboxane A2 Receptor ◽  
Prostacyclin Receptor ◽  
Structure Activity ◽  
Pg E2 ◽  
Intramolecular Hydrogen ◽  
Related Compounds

TRA-418, a thromboxane A2 receptor antagonist and prostacyclin receptor agonist, inhibits platelet-leukocyte interaction in human whole blood

2010 ◽  
Vol 104 (10) ◽  
pp. 788-795 ◽  
Author(s):  
Michihiro Ohno ◽  
Naohiro Yamada ◽  
Atsushi Ohtake ◽  
Teruo Matsushita ◽  
Mitsuko Miyamoto
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Thromboxane A2 ◽  
Inhibitory Effects ◽  
Antithrombotic Agent ◽  
Thromboxane A2 Receptor ◽  
Beraprost Sodium ◽  
Prostacyclin Receptor ◽  
Tp Receptor ◽  
Ip Receptor

SummaryTRA-418, a compound with both thromboxane A2 receptor (TP receptor) antagonistic and prostacyclin receptor (IP receptor) agonistic activities, was synthesised in our laboratory as a new antithrombotic agent. In this study, we examined the effects of TRA-418 on platelet-leukocyte interactions in human whole blood. Platelet-leukocyte interactions were induced by U-46619 in the presence of epinephrine (U-46619 + epinephrine) or with thrombin receptor agonist peptide 1–6 (TRAP). Platelet-leukocyte interactions were assessed by flow cytometry, with examination of both platelet-neutrophil and platelet-monocyte complexes. In a control experiment, the TP receptor antagonist SQ-29548 significantly inhibited the induction of platelet-leukocyte complexes by the combination of U-46619 and epinephrine, but not TRAP-induced formation of platelet-leukocyte complexes. Conversely, the IP receptor agonist beraprost sodium inhibited platelet-leukocyte complex formation induced by both methods, although the IC50 values of beraprost sodium for U-46619 + epinephrine were at least 10-fold greater than for TRAP. Under such conditions, TRA-418 inhibited both U-46619 + epinephrine-induced and TRAP-induced platelet-leukocyte complex formation in a concentration-dependent manner, in a similar range. These results suggest that TRA-418 exerts its inhibitory effects on platelet-leukocyte interactions by acting as a TP receptor antagonist as well as an IP receptor agonist in an additive or synergistic manner. These inhibitory effects of TRA-418 on formation of platelet-leukocyte complexes suggest the compound is beneficial effects as an antithrombotic agent.

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