Influence of histamine H3-antagonists on human leukocytes

To determine the role of the histamine H₃-receptor on basophils, different specific H₃-antagonists were investigated. Incubation of washed leukocytes with N-acylated histamine-derivatives (N-ahd) induced elevated histamine levels. This process turned out to be dependent on dose, time and temperature, but independent of Ca²⁺ and Mg²⁺ ions. IgE-mediated histamine release was not modulated. ³H]-l-histidine was not decarboxylated into ³H]-histamine in spite of the observed histamine increase. Highly purified basophils did not show any histamine elevation but purified neutrophils and eosinophils were found to have increased histamine levels even after disintegration and subsequent incubation with N-ahd. It seems that the increased histamine levels result from the cleavage of the applied histamine amides. Other potent H₃-antagonists (e.g. thioperamide) neither produced increased histamine levels nor influenced IgE-mediated release from basophil leukocytes. The existence of H₃-receptors on human basophils therefore seems unlikely.This work was supported by Grant No. KI 622/1-1 from the Deutsche Forschungsgemeinschaft, Bonn, FRG.