Chansel D, Béa M L, Ardaillou R
INSERM 64, Hôpital Tenon, Paris, France.
Mol Cell Endocrinol. 1989 Apr;62(2):263-71. doi: 10.1016/0303-7207(89)90013-0.
Modulation of renin synthesis by lipoxygenase products has been studied in cultured human mesangial cells under basal conditions and in the presence of prostaglandin (PG) E2. Total renin and cyclic AMP productions were stimulated in a dose-dependent manner (0.1-10 microM) by PGE2. The stimulatory effect of PGE2 on renin production was inhibited by 12-hydroxyeicosatetraenoic acid (12-HETE) between 0.1 and 100 nM. Extracellular and intracellular renin were affected similarly. Neither basal and PGE2-dependent cyclic AMP nor basal cyclic GMP productions were modified. 15-Hydroxyeicosatetraenoic acid (15-HPETE), 12-hydroperoxyeicosatetraenoic acid (12-HPETE) and 15-hydroperoxyeicosatetraenoic acid (15-HPETE) had the same effects as 12-HETE. Intracellular calcium concentration was not modified in the presence of 12-HETE. Since oleyl-2-acetylglycerol (OAG), an analog of diacylglycerol, also inhibited PGE2-stimulated renin production, it is hypothesized that the effect of the lipoxygenase products is mediated via protein kinase C stimulation.
在基础条件下以及存在前列腺素(PG)E2的情况下,已对培养的人系膜细胞中脂氧合酶产物对肾素合成的调节作用进行了研究。PGE2以剂量依赖性方式(0.1 - 10微摩尔)刺激总肾素和环磷酸腺苷(cAMP)的产生。0.1至100纳摩尔的12 - 羟基二十碳四烯酸(12 - HETE)抑制了PGE2对肾素产生的刺激作用。细胞外和细胞内肾素受到的影响相似。基础的和PGE2依赖的cAMP以及基础的环磷酸鸟苷(cGMP)产生均未改变。15 - 羟基二十碳四烯酸(15 - HPETE)、12 - 氢过氧二十碳四烯酸(12 - HPETE)和15 - 氢过氧二十碳四烯酸(15 - HPETE)与12 - HETE具有相同的作用。在存在12 - HETE的情况下,细胞内钙浓度未改变。由于二酰基甘油类似物油酰 - 2 - 乙酰甘油(OAG)也抑制PGE2刺激的肾素产生,因此推测脂氧合酶产物的作用是通过蛋白激酶C刺激介导的。