Copyright 0 1981 by The American Society for Pharmacology and Experimental Therapeutics p,.j,,jj j,, Cyclic AMP Agonist Inhibition Increases at Low Levels of Histamine Release from

Ronald S. Tung and Lawrence M. Lichtenstein: Cyclic AMP cyclic AMP, all act by increasing the cyclic AMP level. Each agonist inhibition increases at low levels of histamine release agonist was 1 0- to 1 000-fold more potent (relative ID50) at low from human basophils. J. Pharmacol. Exp. Ther. 218: 642- levels of histamine release (5-1 0 % of total histamine) than at 646, 1 981. high levels (50-80%). Thus, the inhibitory potential of a drug is a function of the concentration of antigen used to initiate the The relationship between the intensity of the signal for antigen- response. Our results are now more in accord with the inhibi-induced immunoglobulin E-mediated histamine release from tory profile of these drugs in human lung tissue. It is suggested human basophils and the concentration of agonist needed to that in vivo release is likely to be low and that this is the level inhibit release has been determined. The agonists, prostaglan- at which to evaluate drugs in vitro. din E1, dimaprit, fenoterol, isobutylmethylxanthine and dibutyryl Histamine release from the basophils of mixed leukocytes dose required to exert the same result in leukocytes is greater and from the mast cells of chopped lung preparations are well than 10 M. studied in vitro models of allergic phenomena (Lichtenstein Consequently, the present study asked whether there was a and Osler, 1964; Kaliner and Austen, 1975). Release in both relationship between the inhibition by cAMP active drugs an