Interaction of the antiallergic agent AA-344 with biogenic amines and prostaglandins in production of cyclic AMP in rat mast cells.
AA-344, which has been evidenced to inhibit selectively IgE-mediated allergic reactions, exhibited an inhibitory effect on cyclic AMP phosphodiesterase (PDase) in the homogenates of purified rat peritoneal mast cells (RMC). AA-344 showed synergistic effects with epinephrine, isoproterenol or prostaglandin E2 and F2 alpha in increasing cyclic AMP level in RMC: the combinations caused an increase in cyclic AMP 30-160 times as much as that caused by the respective agent alone. In the latter effect, AA-344 was at least 1,000 times as potent as theophylline. On the other hand, histamine or serotonin with or without AA-344 had no effect on the RMC cyclic AMP. These results obtained in vitro suggest that AA-344 may exert antiallergic action by increasing cyclic AMP via an interaction with epinephrine or prostaglandins which might be endogenously involved in regulation of a function of RMC in allergic reactions.
D000588:Amines / Q000494:pharmacology*; D000818:Animals; D002867:Chromones / Q000494:pharmacology / Q000627:therapeutic use*; D000242:Cyclic AMP / Q000096:biosynthesis; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006967:Hypersensitivity / Q000188:drug therapy*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use; D013806:Theophylline / Q000494:pharmacology
D000588:Amines; D002867:Chromones; D010726:Phosphodiesterase Inhibitors; D011453:Prostaglandins; D013777:Tetrazoles; D012701:Serotonin; C018537:6-ethyl-3-(1H-tetrazol-5-yl)chromone; D006632:Histamine; D013806:Theophylline; D000242:Cyclic AMP; D007545:Isoproterenol; D004837:Epinephrine