Interaction of the Antiallergic Agent AA-344 with Biogenic Amines and Prostaglandins in Production of Cyclic AMP in Rat Mast Cells

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Abstract
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 F2α 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.