Inhibition of adenylate cyclase in perfusion mouse palate by secalonic acid D.
Inhibition of adenylate cyclase in perfusion mouse palate by secalonic acid D.
复制标题
癸二酸 D 抑制灌注小鼠上颚中的腺苷酸环化酶。
DOI：
10.1080/15287399409531835
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Reddy,CS
中科院分区：
文献类型：
--
作者：
Reddy,RV;Eldeib,MM;Reddy,CS
糖皮质激素（GC）诱导暴露孕鼠子代腭裂（CP）。糖皮质激素通过减少花生四烯酸（AA）从膜上的释放来抑制前列腺素（PG）的合成，这是由抑制磷脂酶A2引起的。这种代谢事件与妊娠前阶段（妊娠第13天）腭cAMP水平降低有关。真菌毒素secalonic acid D （SAD）诱导经治疗的母亲所生的后代CP，升高母亲血浆皮质酮水平，降低融合前腭cAMP水平。此外，在融合后（妊娠第15天），cAMP升高。由于外源性AA同时给予GC暴露的母亲可能保护后代免受GC诱导的CP，因此对SAD进行了这种可能性的测试。妊娠CD1小鼠在妊娠第11天给予致畸剂量的SAD (30 mg/kg, ip)，同时给予最大耐受剂量的AA （200 mg/kg, sc，妊娠第11、12和13天）。长期来看，AA治疗并没有显著降低SAD诱导的CP。为了评估SAD诱导的腭cAMP改变是否由于融合前和融合后腭膜相关腺苷酸环化酶（AC）活性的降低，在妊娠期13.5至15.5之间每隔12小时处死经SAD处理的母亲，收集胎儿的腭架，在存在或不存在酶刺激剂氟化钠（NaF）的情况下测定AC活性（cAMP形成/mg蛋白/分钟）。虽然SAD没有改变未刺激的AC活性，但它显著降低了NaF诱导的预灌注期酶活性的刺激。这种抑制不能被孵育混合物中过量的GTP逆转。由于NaF刺激AC表明涉及GTP结合单元和催化单元的受体后位点功能，并且由于GTP的添加未能纠正SAD诱导的NaF刺激酶的改变，因此表明SAD可能通过其对催化单元的影响以不影响酶基础活性的方式抑制AC对刺激的敏感性。
Glucocorticoids (GC) induce cleft palate (CP) in the offspring of exposed pregnant mice. Glucocorticoids induce prostaglandin (PG) synthesis inhibition via reduced arachidonic acid (AA) release from membranes, and this results from inhibition of phospholipase A2. This metabolic event is associated with reduced palatal cAMP levels in the prefusion stages (d 13 of gestation). The mycotoxin secalonic acid D (SAD) induces CP in the offspring born to treated mothers, elevates maternal plasma corticosterone levels, and reduces prefusion palatal cAMP levels. In addition, an increase in cAMP was noted in the postfusion period (d 15 of gestation). Since exogenous AA given simultaneously to GC‐exposed mothers may protect against GC‐induced CP in the offspring, such a possibility was tested for SAD. Pregnant CD1 mice given a teratogenic dose of SAD (30 mg/kg, ip, on gestational d 11) were simultaneously treated with maximal tolerated doses of AA (200 mg/kg, sc, on gestational d 11, 12, and 13). At term, no significant reduction in SAD‐induced CP was seen as a result of AA treatment. To evaluate if SAD‐induced alterations in palatal cAMP are due to reduced palatal membrane‐associated adenylate cyclase (AC) activity during pre‐ and postfusion periods, SAD‐treated mothers were sacrificed at 12‐h intervals between gestational d 13.5 and 15.5, palate shelves were collected from the fetuses, and AC activity (cAMP formed/mg protein/min) was assayed in the presence or absence of the enzyme stimulator, sodium fluoride (NaF). Although SAD did not alter unstimulated AC activity, it significantly reduced the NaF‐induced stimulation of enzyme activity in the prefusion period. This inhibition could not be reversed by excess GTP in the incubation mixture. Since NaF stimulation of AC indicates post‐receptor‐site function involving GTP‐binding and catalytic units, and since addition of GTP failed to correct SAD‐induced alteration of NaF stimulation of the enzyme, it is suggested that SAD may inhibit the AC sensitivity to stimuli by its effect on the catalytic unit in a manner that does not affect enzymic basal activity.