Schiff L J, Moore S J
In Vitro Cell Dev Biol. 1985 Dec;21(12):688-92. doi: 10.1007/BF02620923.
The ability of cyclic AMP-elevating agents to induce normal differentiation has been investigated in retinoid-deficient hamster tracheal epithelium in organ culture. Dibutyryl cAMP (dbcAMP) and other cAMP-regulating agents alone caused disappearance of keratin and regeneration of normal mucociliary epithelium in retinoid-deficient cultures. Incubation of retinoid-deficient cultures with dbcAMP, isoproterenol, and cholera toxin (CT) (without addition of exogenous retinoid) reversed keratinization in a dose-dependent manner. The ED50 of cultures treated with dbcAMP was 4 X 10(-6) M; ED50 of isoproterenol was 7 X 10(-5) M; and CT, 0.6 micrograms/ml. Phosphodiesterase inhibitors and other cAMP analogs were inactive. Dibutyryl cAMP in combination with theophylline enhanced normal differentiation. Retinoid-deficient tracheas pretreated for 20 h with 10(-9) M all-trans-retinoic acid (RA) responded to 10(-6) M dbcAMP by potentiating normal differentiation; this concentration of dbcAMP alone was inactive. Isoproterenol showed a similar response but to a lesser degree. These cAMP-elevating agents applied in combination with theophylline did not increase activity.
在器官培养的维生素A缺乏的仓鼠气管上皮中，研究了环磷酸腺苷（cAMP）升高剂诱导正常分化的能力。单独使用二丁酰环磷腺苷（dbcAMP）和其他cAMP调节剂可导致维生素A缺乏培养物中的角蛋白消失，并使正常的黏液纤毛上皮再生。将维生素A缺乏的培养物与dbcAMP、异丙肾上腺素和霍乱毒素（CT）一起孵育（不添加外源性维生素A）可呈剂量依赖性地逆转角质化。用dbcAMP处理的培养物的半数有效剂量（ED50）为4×10^(-6)M；异丙肾上腺素的ED50为7×10^(-5)M；CT为0.6微克/毫升。磷酸二酯酶抑制剂和其他cAMP类似物无活性。dbcAMP与茶碱联合使用可增强正常分化。用10^(-9)M全反式维甲酸（RA）预处理20小时的维生素A缺乏的气管对10^(-6)M dbcAMP有反应，通过增强正常分化；单独使用该浓度的dbcAMP无活性。异丙肾上腺素表现出类似的反应，但程度较小。这些cAMP升高剂与茶碱联合使用并未增加活性。
