Distinct effects of z-335, a new thromboxane A2 receptor antagonist, on rabbit platelets and aortic smooth muscle.

Abstract

The effect of a novel thromboxane A2 receptor (TP) antagonist, (+/-)-sodium[2-(4-chlorophenylsulfonylaminomethyl)- indan-5-yl]acetate monohydrate (Z-335), on the U46619-induced responses was compared between rabbit platelets and aorta. Z-335 inhibited platelet shape change induced by U46619 with higher efficacy than SQ29548, a common TP antagonist. The U46619-induced platelet aggregation was inhibited by Z-335 in a noncompetitive manner, while it was competitively inhibited by SQ29548. Z-335 inhibited U46619-induced vasoconstriction of rabbit aorta with higher efficacy than SQ29548. The pA2 value of Z-335 in aortic vasoconstriction was significantly higher than in platelet shape change. The competitive binding study showed the higher pKi value of Z-335 against [3H]-SQ29548 binding in rabbit aortic smooth muscle cells than in platelets. These data suggest that Z-335 has useful characteristics of TP antagonism.

Cite this paper

@article{Yoshida2007DistinctEO, title={Distinct effects of z-335, a new thromboxane A2 receptor antagonist, on rabbit platelets and aortic smooth muscle.}, author={Makoto A Yoshida and Yukari Sato and Tokuro Shimura and Satoko Ohkubo and Shigeyoshi Honma and Takao Tanaka and Tadashi Kurimoto and Norimichi Nakahata}, journal={Pharmacology}, year={2007}, volume={79 1}, pages={50-6} }