Secalonic acid D-induced changes in palatal cyclic AMP and cyclic GMP in developing mice.
Secalonic acid D-induced changes in palatal cyclic AMP and cyclic GMP in developing mice.
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癸二酸 D 诱导发育小鼠腭环 AMP 和环 GMP 的变化。
DOI：
10.1002/tera.1420370408
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Reddy,CS
中科院分区：
文献类型：
--
作者：
Eldeib,MM;Reddy,CS
Secalonic acid D（SAD）通过一种未知的机制诱导发育中小鼠的腭裂。为了研究环核苷酸（cAMP和cGMP）在SAD致畸中的可能作用，测定了胎龄130 - 1612（白天）胎儿腭提取物中cAMP和cGMP的水平。从妊娠第110天接受5%（重量/重量）处理的妊娠CD-1小鼠中获得胎儿卷）碳酸氢钠（NaHCO3，对照）或30 mg/kg SAD的5%NaHCO3溶液，腹膜内（i.p.）。采用放射免疫法定量测定环核苷酸水平。对照组cAMP水平在妊娠第1412天达到峰值。SAD组在妊娠第1312天和第1400天cAMP水平显著降低，在妊娠第1300天至第1400天总cAMP水平降低30%，在第1412天达到峰值时变化很小或没有变化。然而，在第1512天，SAD组的腭部cAMP水平比对照组增加了68%。cGMP的控制水平似乎遵循昼夜模式，在黑暗周期结束时达到最大水平。SAD组cGMP水平在第1312天下降31%（P <0.05），第150天上升100%（P <0.01）。在妊娠150~1612天，cGMP总量比对照组高33%（P <0.01）。SAD组中对照组（140 - 1612）在腭闭合后的所有时间点上的裂数均显著高于对照组（P <0.01 - 0.005），数值范围为20%-34%，而对照组为0%。第130天至第150天的形态学变化表明SAD处理胎仔的中腭和后腭区域的搁板抬高失败。这些结果表明，SAD诱导腭裂与体内既定环核苷酸模式的动态变化（最初减少，随后增加）相关，并支持环核苷酸介导的细胞过程在正常和异常腭发育中的机制作用。
Secalonic acid D (SAD) induces cleft palate in the developing mouse by an unknown mechanism. To investigate possible roles of cyclic nucleotides (cAMP and cGMP) in the teratogenesis of SAD, cAMP and cGMP levels were measured in the extracts of fetal palates of gestational age 130through 1612(dayshours). Fetuses were obtained from pregnant CD‐1 mice treated on day 110of gestation, with either 5% (wt./vol.) sodium bicarbonate (NaHCO3, control) or 30 mg/kg of SAD in 5% NaHCO3, intraperitoneally (i.p.). Radioimmunoassay was used to quantitate cyclic nucleotide levels. Cyclic AMP levels peaked on day 1412of gestation in controls. In the SAD group there was a significant decrease in cAMP levels on days 1312and 140of gestation and a decrease of 30% in total cAMP on days 130through 140of gestation, with little or no change at the peak on day 1412. On day 1512, however, the SAD group had a 68% increase in palatal cAMP level over the control. Control levels of cGMP appeared to follow a diurnal pattern reaching maximal levels at the end of the dark cycle. In contrast, SAD decreased the cGMP level by 31% on day 1312(P< 0.05) and increased it 100% above that of the control level on day 150(P< 0.01). Total cGMP during days 150through 1612of gestation was 33% higher than control (P< 0.01). The number of clefts in the SAD group was significantly higher at all points following palate closure in the control fetuses (140through 1612) with values ranging from 20% to 34% versus 0% in the control (P< 0.01–0.005). Morphological changes on days 130through 150indicated a failure of shelf elevation in middle and posterior palatal regions of SAD‐treated fetuses. These results suggest that the induction of cleft palate by SAD is associated with dynamic changes (initial decrease followed by later increase), in vivo, in established cyclic nucleotide patterns and support a mechanistic role for cyclic nucleotide‐mediated cellular processes in normal as well as abnormal palate development.