Naze S, Le Stunff H, Dokhac L, Thomas G, Harbon S
Endocrinologie et Régulations Cellulaires, CNRS URA 1131, Université Paris Sud, Orsay, France.
J Pharmacol Exp Ther. 1997 Apr;281(1):15-23.
In rat myometrium labeled with [3H]myristic acid, endothelin (ET)-1 via ET(A) receptors stimulated, in the presence of 0.3% butanol, the formation of [3H]phosphatidylbutanol ([3H]PBut) as a result of phospholipase D activity. Fluoroaluminates increased [3H]PBut generation, which indicated that a heterotrimeric G protein was involved. The ET-1 effect was insensitive to pertussis toxin and was rapidly desensitized. The calcium ionophore ionomycin as well as 4beta-phorbol 12-myristate-13-acetate and 4beta-phorbol 12,13-dibutyrate also stimulated [3H]P-But production. Protein kinase C (PKC) inhibition, particularly with Ro-31-8220, and down-regulation of PKC by 4beta-phorbol 12-myristate-13-acetate, abrogated 4beta-phorbol 12,13-dibutyrate responses but partially reduced (50%) ET-1 and ionomycin stimulatory effects. [3H]PBut production induced by ionomycin depended on Ca++ influx, whereas that induced by 4beta-phorbol 12,13-dibutyrate did not. Decrease of extracellular Ca++ partially reduced (60%) ET-1 stimulation that was additionally attenuated (75%) by chelerythrine, a PKC inhibitor. The data indicate that in myometrium, phospholipase D was activated by PKC and Ca++, which both contribute at least partially to ET-1-mediated phospholipase D activation.
在用[3H]肉豆蔻酸标记的大鼠子宫肌层中，内皮素（ET）-1通过ET(A)受体，在0.3%丁醇存在的情况下，由于磷脂酶D的活性刺激了[3H]磷脂丁醇（[3H]PBut）的形成。氟铝酸盐增加了[3H]PBut的生成，这表明涉及一种异源三聚体G蛋白。ET-1的作用对百日咳毒素不敏感且迅速脱敏。钙离子载体离子霉素以及4β-佛波醇12-肉豆蔻酸酯-13-乙酸酯和4β-佛波醇12,13-二丁酸酯也刺激了[3H]P-But的产生。蛋白激酶C（PKC）的抑制，特别是用Ro-31-8220，以及4β-佛波醇12-肉豆蔻酸酯-13-乙酸酯对PKC的下调，消除了4β-佛波醇12,13-二丁酸酯的反应，但部分降低了（50%）ET-1和离子霉素的刺激作用。离子霉素诱导的[3H]PBut产生依赖于Ca++内流，而4β-佛波醇12,13-二丁酸酯诱导的则不依赖。细胞外Ca++的减少部分降低了（60%）ET-1的刺激，PKC抑制剂白屈菜红碱使其进一步减弱（75%）。数据表明，在子宫肌层中，磷脂酶D由PKC和Ca++激活，它们至少部分地共同促成了ET-1介导的磷脂酶D激活。
