Stimulation by Bt2cAMP of epidermal mucous metaplasia in retinol-pretreated chick embryonic cultured skin, and its inhibition by herbimycin A, an inhibitor for protein-tyrosine kinase.
Epidermal mucous metaplasia of cultured 13-day-old chick embryonic tarsometatarsal skin can be induced by culture in medium containing retinol (20 microM) for only 8-24 h and then in a chemically defined medium without vitamins or serum for 6 days. In the induction of mucous metaplasia, retinol primarily affects the dermal cells and a signal(s) induced in the dermis by excess retinol alters epidermal differentiation toward secretory epithelium. In this work we found that Bt2cAMP (2 mM) stimulated mucous metaplasia severalfold when added to retinol-pretreated skin but inhibited epidermal mucous metaplasia when added together with retinol. Forskolin (100 microM), an activator of adenylate cyclase, also stimulated mucous metaplasia when added to retinol-pretreated skin. On the other hand, transduction in the epidermal cells of a signal(s) induced in dermal cells by excess retinol was inhibited by herbimycin A (500 ng/ml), an inhibitor of protein-tyrosine kinases, and TPA (0.1 microM), an activator of protein kinase C. Hence these findings indicated that cAMP stimulated signal-induced mucous metaplasia, and that transduction of the signal(s) in the epidermal cells required protein-tyrosine kinase and was inhibited by protein kinase C.
Obinata
A
A
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Akimoto
Y
Y
Hirano
H
H
Endo
H
H
D000262:Adenylyl Cyclases / Q000187:drug effects; D000818:Animals; D016227:Benzoquinones; D003994:Bucladesine / Q000494:pharmacology*; D002642:Chick Embryo; D051152:Clusterin; D005576:Colforsin / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000187:drug effects; D004817:Epidermis / Q000187:drug effects; D006023:Glycoproteins / Q000096:biosynthesis; D047029:Lactams, Macrocyclic; D008679:Metaplasia / Q000139:chemically induced; D018832:Molecular Chaperones; D009092:Mucous Membrane / Q000473:pathology; D009924:Organ Culture Techniques; D011493:Protein Kinase C / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000494:pharmacology*; D017828:Rifabutin / Q000031:analogs & derivatives; D012867:Skin / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014801:Vitamin A / Q000494:pharmacology*
D016227:Benzoquinones; D051152:Clusterin; D006023:Glycoproteins; D047029:Lactams, Macrocyclic; D018832:Molecular Chaperones; D011809:Quinones; D014801:Vitamin A; D005576:Colforsin; D017828:Rifabutin; D003994:Bucladesine; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate