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Cannabinoids stimulate prostaglandin production by human gestational tissues through a tissue- and CBl-receptor-specific mechanism

机译:大麻素通过组织和CB1受体特异性机制刺激人类妊娠组织产生前列腺素

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First published November 27, 2007; doi:10.1152/ajpendo.00495.2007.-Endocannabinoids have been implicated in the mechanisms of implantation, maintenance of pregnancy, and parturition in women. Intrauterine prostaglandin production and actions are also critical in each of these mechanisms. Hence, we have evaluated the effects of cannabinoids on prostaglandin biosynthesis by human gestational membranes. Explants of term amnion and choriodecidua were established and treated with the endogenous endocannabinoids 2-arachi-donoyl glycerol and anandamide, as well as the synthetic cannabinoid CP55,940, to determine their ability to modulate PGE2 production. The explants were also treated with CP55,940 in the presence of either SR141716A (a potent and selective antagonist of the cannabinoid receptor CB1) or NS398 [a cyclooxygenase (COX)-2 inhibitor] to determine whether any observed stimulation of PGE2 production was mediated through the CBl-receptor and/or COX-2 activity. All three cannabinoids caused a significant increase in PGE2 production in the amnion but not in the choriodecidua. However, separated fetal (chorion) explants responded to cannabinoid treatment in a similar manner to amnion, whereas maternal (decidual) explants did not. The enhanced PGE2 production caused by CP55,940 was abrogated by cotreatment with either SR141716A or NS398, illustrating that the cannabinoid action on prostaglandin production in fetal membranes is mediated by CB1 agonism and COX-2. Data from Western blotting show that cannabinoid treatment results in the upregulation of COX-2 expression. This study demonstrates a potential role for endocannabinoids in the modulation of prostaglandin production in late human pregnancy, with potentially important implications for the timing and progression of term and preterm labor and membrane rupture.
机译:首次发布于2007年11月27日; doi:10.1152 / ajpendo.00495.2007.-内源性大麻素与妇女的着床,维持妊娠和分娩有关。宫内前列腺素的产生和作用在这些机制中也很重要。因此,我们评估了大麻素对人胎膜对前列腺素生物合成的影响。建立足月羊膜和绒毛膜蜕膜的外植体,并用内源性内源性大麻素2-花生四烯酸甘油酯和anandamide,以及合成的大麻素CP55,940进行处理,以确定它们调节PGE2产生的能力。还用CP55,940在SR141716A(大麻素受体CB1的有效和选择性拮抗剂)或NS398(环加氧酶(COX)-2抑制剂)存在下,用CP55,940处理外植体,以确定是否观察到了对PGE2产生的任何刺激通过CB1受体和/或COX-2活性。所有这三种大麻素均导致羊膜中PGE2的产生显着增加,但脉络膜蜕膜中却没有。但是,分离的胎儿(绒毛)外植体对大麻素的处理方式与羊膜相似,而孕妇(蜕膜)外植体则没有。通过与SR141716A或NS398共同处理消除了由CP55,940引起的PGE2产量增加,这说明大麻素对胎膜中前列腺素产生的作用是由CB1激动作用和COX-2介导的。 Western印迹数据表明,大麻素处理可导致COX-2表达上调。这项研究表明内源性大麻素在人类晚期妊娠中在调节前列腺素产生中的潜在作用,对足月和早产的时间和进程以及胎膜破裂具有潜在的重要意义。

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