Nakajima M, Ueda M
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Eur J Pharmacol. 1990 Dec 4;191(3):359-68. doi: 10.1016/0014-2999(90)94169-x.
U46619, a stable thromboxane A2 (TXA2) mimetic, and prostaglandin F2 alpha (PGF2 alpha) contracted helical strips of cat coronary, renal and mesenteric arteries in a concentration-dependent manner. The EC50 values for U46619 did not differ significantly in these arteries, but those for PGF2 alpha were in the order of coronary less than renal less than mesenteric arteries. Contractions induced by U46619 were antagonized by S-145, a selective TXA2 receptor antagonist, with similar activity in these arteries. On the other hand, contractions induced by low concentrations of PGF2 alpha (10(-9) to 10(-7) M) were not influenced by treatment with S-145 in coronary arteries, although those induced by high concentrations (5 x 10(-7) to 10(-5) M) were partially attenuated. These contractions resistant to the TXA2 antagonist were antagonized by diphloretin phosphate (DPP), a non-selective PG antagonist. Contractions induced by PGF2 alpha (5 x 10(-7) to 5 x 10(-5) M) in mesenteric arteries were inhibited by S-145 in a concentration-dependent manner. Contractions induced by PGF2 alpha in renal arteries were partially inhibited by S-145. The inhibitory activity of S-145 to PGF2 alpha-induced contractions at EC50 was in the order of coronary less than renal less than mesenteric arteries. Treatment with indomethacin slightly potentiated the contractions induced by PGF2 alpha in mesenteric arteries. Removal of the endothelium did not affect the contractile responses induced by PGF2 alpha and the inhibitory activity of S-145 in the arteries. These results suggest that the contractile responses induced by low concentrations of PGF2 alpha (up to 10(-7) M) are associated with their action via PG receptor(s), which is different from TXA2 receptor, and those induced by high concentrations of PGF2 alpha (5 x 10(-7) M or higher) interact with TXA2 receptors in cat vascular smooth muscles. It appears that the functional expression of this PG receptor(s) is greater in coronary arteries than in renal arteries, and that it is not found in mesenteric arteries.
U46619是一种稳定的血栓素A2（TXA2）类似物，前列腺素F2α（PGF2α）能使猫的冠状动脉、肾动脉和肠系膜动脉的螺旋条以浓度依赖的方式收缩。U46619在这些动脉中的半数有效浓度（EC50）值无显著差异，但PGF2α的EC50值顺序为冠状动脉＜肾动脉＜肠系膜动脉。U46619诱导的收缩可被选择性TXA2受体拮抗剂S-145拮抗，在这些动脉中具有相似的活性。另一方面，低浓度PGF2α（10⁻⁹至10⁻⁷M）诱导的冠状动脉收缩不受S-145处理的影响，尽管高浓度（5×10⁻⁷至10⁻⁵M）诱导的收缩会部分减弱。这些对TXA2拮抗剂有抗性的收缩可被非选择性PG拮抗剂磷酸二氢杨梅素（DPP）拮抗。PGF2α（5×10⁻⁷至5×10⁻⁵M）在肠系膜动脉中诱导的收缩被S-145以浓度依赖的方式抑制。PGF2α在肾动脉中诱导的收缩被S-145部分抑制。S-145在EC50时对PGF2α诱导收缩的抑制活性顺序为冠状动脉＜肾动脉＜肠系膜动脉。吲哚美辛处理略微增强了PGF2α在肠系膜动脉中诱导的收缩。去除内皮不影响PGF2α诱导的收缩反应以及S-145在动脉中的抑制活性。这些结果表明，低浓度PGF2α（高达10⁻⁷M）诱导的收缩与其通过PG受体（不同于TXA2受体）的作用相关，而高浓度PGF2α（5×10⁻⁷M或更高）诱导的收缩在猫血管平滑肌中与TXA2受体相互作用。似乎这种PG受体的功能表达在冠状动脉中比在肾动脉中更强，且在肠系膜动脉中未发现。
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