Effects of Cyclic Adenosine 3' :5'-Monophosphate-Elevating Agents and Retinoic Acid on Differentiation in Retinoid-Deficient Tracheal Cultures

• Published in: In Vitro Cellular & Developmental Biology 1985-12, Vol.21 (12), p.688-692
• Main Authors: Schiff, Leonard J., Moore, Steven J.
• Format: Article
• Language: English
• Subjects: 1-Methyl-3-isobutylxanthine - pharmacology; Animals; Biological and medical sciences; Bucladesine - pharmacology; Cell Differentiation - drug effects; Cell differentiation, maturation, development, hematopoiesis; Cell lines; Cell physiology; Cells, Cultured; Cholera; Cholera Toxin - pharmacology; Cricetinae; Cyclic AMP - metabolism; Dose-Response Relationship, Drug; Drug Synergism; Epithelium; Fundamental and applied biological sciences. Psychology; Isoproterenol - pharmacology; Keratinization; Keratins; Keratins - metabolism; Molecular and cellular biology; Organ culture techniques; Phosphodiesterase inhibitors; Phosphodiesterase Inhibitors - pharmacology; Retinoids; Retinoids - deficiency; Theophylline - pharmacology; Toxins; Trachea; Trachea - cytology; Trachea - metabolism; Tretinoin - pharmacology
• ISSN: 0883-8364; 2327-431X; 1475-2689
• 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 ED50of cultures treated with dbcAMP was$4 \times 10^{-6} M$; ED50of isoproterenol was$7 \times 10_{-5} M$; and CT,$0.6 \mug/ml$. 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 10-6M 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.