Modulation of pig epidermal adenylate-cyclase responses by protein-synthesis inhibitors: its relation to glucocorticoid and colchicine effects.
The effects of protein-synthesis inhibitors (actinomycin D, puromycin, and cycloheximide) on epidermal adenylate-cyclase responses were investigated. When pig skin (epidermis) was incubated in RPMI-1640 medium, the beta-adrenergic adenylate-cyclase response (epinephrine-induced cyclic-AMP accumulations) decreased, whereas the adenosine and histamine responses increased after long-term (up to 48 h) incubation. The addition of actinomycin D or puromycin to the incubation medium resulted in a marked increase in epinephrine-induced cyclic-AMP accumulations and a decrease in adenosine- and histamine-induced cyclic-AMP accumulations. Cycloheximide had a weak effect on the epinephrine response, and had apparently stronger effects on the adenosine and histamine responses than actinomycin D or puromycin. Histologically, various degenerative changes of keratinocytes (with or without acantholytic changes) were observed after long-term incubation with these protein-synthesis inhibitors. Both low- and high-Km cyclic-AMP phosphodiesterase activities were moderately decreased by the protein-synthesis inhibitors. However, augmentation effects on the beta-adrenergic response were also observed in the presence of the cyclic-AMP phosphodiesterase inhibitor, theophylline. We have described previously similar augmentation effects on the beta-adrenergic response caused by glucocorticoids and colchicine. Comparison of the effects of these chemicals with those of protein-synthesis inhibitors revealed that the most marked effects on the beta-adrenergic response were produced by actinomycin D, puromycin and colchicine; glucocorticoid had a moderate effect (hydrocortisone), while cycloheximide had only a weak effect.(ABSTRACT TRUNCATED AT 250 WORDS)
D000241:Adenosine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D003078:Colchicine / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology*; D004817:Epidermis; D004837:Epinephrine / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D011691:Puromycin / Q000494:pharmacology*; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D013552:Swine
D005938:Glucocorticoids; D003609:Dactinomycin; D011691:Puromycin; D006632:Histamine; D003513:Cycloheximide; D000262:Adenylyl Cyclases; D000241:Adenosine; D003078:Colchicine; D004837:Epinephrine