DIFFERENCES IN ACTIVITIES OF THROMBOXANE-A2 RECEPTOR ANTAGONISTS IN SMOOTH-MUSCLE CELLS

被引:14
作者
MIKI, I
KASE, H
ISHII, A
机构
[1] Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., 411, Shimotogari 1188, Nagaizumi, Sunto, Shizuka
来源
EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION | 1992年 / 227卷 / 02期
关键词
THROMBOXANE-A2 PROSTAGLANDIN H-2 RECEPTORS (TXA2 PGH2 RECEPTORS); SMOOTH MUSCLE CELLS (VASCULAR); CA-2+ CONCENTRATIONS (INTRACELLULAR); THROMBOXANE A2 RECEPTOR ANTAGONIST (KW-3635 AND BM-13505);
D O I
10.1016/0922-4106(92)90128-I
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Thromboxane A2/prostaglandin H-2 (TXA2/PGH2) receptors were characterized in rat vascular smooth muscle cells (VSMC). The specific binding of [H-3]SQ 29,548 was inhibited by KW-3635, a novel non-prostanoic TXA2 antagonist, SQ 29,548 and BM-13505 (daltroban). SO 29,548 showed a single class of binding sites with a K(i) value of 1.6 nM. The inhibition patterns were better fit to two-component curves for KW-3635 (K(i) values of 0.45 nM and 42 nM) and BM-13505 (23 nM and 20 nM). U46619, a TXA, agonist, induced an increase in intracellular calcium concentration ([Ca2+]i), which was inhibited by these antagonists. KW-3635 and SQ 29,548 did not induce any increase in [Ca2+]i, whereas BM-13505 was found to induce a smaller increase in [Ca2+]i. The BM-13505-induced increase in [Ca2+]i was also inhibited by pretreatment with KW-3635, SQ 29,548 and BM-13505. The results demonstrate that BM-13505 has partial agonistic activity on TXA2/PGH2 receptors, and KW-3635 and SO 29,548 do not. SQ 29,548 and BM-13505 inhibited both U-46619- and BM-13505-induced increases in [Ca2+]i to a similar degree. Alternatively, KW-3635 inhibited a U46619-induced increase in [Ca2+]i more effectively than a BM-13505-induced increase. These results suggest the heterogeneity of functional binding sites or subtypes of TXA2/PGH2 receptors present in
引用
收藏
页码:199 / 204
页数:6
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