Cantabrana B, Fernandez A, Baamonde A, Andres-Trelles F, Hidalgo A
Department of Medicine, Pharmacology Laboratory, Faculty of Medicine, Oviedo, Spain.
Methods Find Exp Clin Pharmacol. 1991 Apr;13(3):187-92.
The effect of four eicosanoid synthesis inhibitors (ESIs): mepacrine (6 x 10(-6) to 10(-4) M), nordihydroguaiaretic acid (NDHGA, 10(-6) to 10(-5) M), indomethacin (2 x 10(-6) and 2 x 10(-5) M) and imidazole (10(-5) and 10(-4) M), were studied on contractions induced by cumulative doses (4 and 20 mU/ml) of oxytocin (OT) on the uterus of rats both in natural estrus and ovariectomized. ESIs were also assayed on contractions induced by carbachol (10(-4) M) and KCl (60 mM) in rat uterus under natural estrus, and OT (10 mU/ml)-induced contractions in rat uterus incubated in calcium-free EDTA treated medium. Mepacrine, NDHGA and indomethacin, but not imidazol, inhibited in a dose-dependent way contractions induced by OT in the uterus. The effect was higher in ovariectomized than in natural estrus rats. Mepacrine and NDHGA, but not indomethacin or imidazole, inhibited contractions induced by carbachol and relaxed tonic contractions to KCl (60 mM). Mepacrine, NDHG and indomethacin also inhibited tonic contractions by OT in calcium-free EDTA treated medium. Our results suggest that mepacrine, NDHGA and indomethacin, independently of inhibition of eicosanoids synthesis, reduce the entry of extracellular calcium and/or the release of intracellular calcium.
研究了四种类花生酸合成抑制剂（ESIs）：米帕林（6×10⁻⁶至10⁻⁴M）、去甲二氢愈创木酸（NDHGA，10⁻⁶至10⁻⁵M）、吲哚美辛（2×10⁻⁶和2×10⁻⁵M）和咪唑（10⁻⁵和10⁻⁴M）对处于自然发情期和去卵巢大鼠子宫中催产素（OT）累积剂量（4和20 mU/ml）诱导的收缩的影响。还检测了ESIs对自然发情期大鼠子宫中卡巴胆碱（10⁻⁴M）和氯化钾（60 mM）诱导的收缩以及在无钙EDTA处理培养基中孵育的大鼠子宫中OT（10 mU/ml）诱导的收缩的作用。米帕林、NDHGA和吲哚美辛而非咪唑以剂量依赖性方式抑制子宫中OT诱导的收缩。去卵巢大鼠的这种作用比自然发情期大鼠更强。米帕林和NDHGA而非吲哚美辛或咪唑抑制卡巴胆碱诱导的收缩并使氯化钾（60 mM）引起的强直性收缩松弛。米帕林、NDHG和吲哚美辛在无钙EDTA处理培养基中也抑制OT引起的强直性收缩。我们的结果表明，米帕林、NDHGA和吲哚美辛，与抑制类花生酸合成无关，可减少细胞外钙的内流和/或细胞内钙的释放。
