Effects of cyclic adenosine 3':5'-monophosphate-elevating agents and retinoic acid on differentiation in retinoid-deficient tracheal cultures.
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.
L J
LJ
Schiff
S J
SJ
Moore
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007545:Isoproterenol / Q000494:pharmacology; D007633:Keratins / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D012176:Retinoids / Q000172:deficiency*; D013806:Theophylline / Q000494:pharmacology; D014132:Trachea / Q000166:cytology* / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D012176:Retinoids; D014212:Tretinoin; D003994:Bucladesine; D007633:Keratins; D002772:Cholera Toxin; D013806:Theophylline; D000242:Cyclic AMP; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine