Pretreatment of human leukocytes with the new xanthine compound, 3,7-dihydro-1,8-dimethyl-3-phenyl-1H-purine-2,6-dione (D 4026), induced a dose-dependent and statistically significant inhibition of immunoglobulin E-mediated histamine release in the concentration interval 0.1-1000 microM. Histamine release elicited with suboptimum amounts of the triggering agent (anti-IgE or antigen) was inhibited to a greater extent than a release initiated with optimum amounts. At a concentration of 10 microM, D 4026 had at least the same inhibitory effect as 100 microM theophylline. When leukocytes were incubated simultaneously with D 4026 and a histamine H-2 receptor-stimulating drug (histamine or clonidine), the two drugs combined induced an inhibition significantly greater than the sum of their individual inhibitory effects. Only pure additive inhibitory effects were, however, obtained during simultaneous treatment of leukocytes with theophylline and histamine.
Ten β‐adrenoceptor agonists were examined with respect to a) relaxation of pilocarpine‐contracted trachea and depression of contractions of the soleus muscle of the guinea‐pig in vitro and b) counteraction of histamine‐induced bronchospasm and depression of contractions of the soleus muscle of the cat in vivo. There was a close correlation between the results obtained in vitro and results obtained on the corresponding tissues in vivo in spite of the different species used. A close correlation was also observed between effects on airway smooth muscle and on the soleus muscle contractions in vitro as well as in vivo for all compounds examined.
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