Effect of the new theophylline derivatives on degranulation of mast cells and phosphodiesterase activity in smooth muscles.
Effect of the new theophylline derivative (beta-hydroxy-benzylopiperazinopropyl-theophylline), designed as R6 on degranulation of the mast cells from rat mesenteries, was tested in vitro and in vivo. In vitro it was found that R6 significantly inhibited mast cell degranulation induced both by the histamine liberator C 48/80 and by rabbit globulin directed against rat serum proteins. The effect was comparable to that revealed by mepyramine, but much stronger than the effects of DSCG and aminophylline. The influence of R6 on mast cells degranulation was less pronounced in the in vivo systems. It was demonstrated by histochemical methods that R6 did not change activity of lactic and succinic dehydrogenases, neither activity of lysosomal hydrolases. In separate system including small intestine from rat it was shown that R6 inhibited activity of the phosphodeisterase in smooth muscles. It was suggested that the effect of R6 on mast cells degranulation is mediated by an increase in cAMP as well as by indirect influence on Ca++ influx.
D000818:Animals; D002478:Cells, Cultured; D004205:Cromolyn Sodium / Q000494:pharmacology; D003470:Culture Media; D003864:Depression, Chemical; D004336:Drug Antagonism; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D008643:Mesentery / Q000166:cytology*; D009130:Muscle, Smooth / Q000201:enzymology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000037:antagonists & inhibitors / Q000494:pharmacology
D003470:Culture Media; D010726:Phosphodiesterase Inhibitors; C028101:7-(beta-hydroxy-gamma-benzylpiperazinopropyl)theophylline; D003189:p-Methoxy-N-methylphenethylamine; D013806:Theophylline; D004205:Cromolyn Sodium