Pharmacologic control of histamine release from human basophils induced by platelet- activating factor

We studied the effect of several compounds that influence different cell activation steps on platelet-activating factor (PAF)-induced basophil histamine secretion. Isobutylmethylxanthine (1-100 μM), dimaprit (1-100 μM) and dibuty- ryl adenosine 3',5'-cyclic phosphate (cAMP; 0.01-1 mM), that increase intracellular cAMP levels, concentration-dependently inhibited PAF-elicited histamine release. Rolipram (phosphodiesterase, PDE, isotype IV inhibitor; 0.1 nM-10 μΜ) potently inhibited histamine secretion activated by PAF, whereas SKF 95654 (PDE III inhibitor; 0.01-10 μΜ) was ineffective. The kinase inhibitor, staurosporine (0.1-100 nM), enhanced PAF-induced basophil histamine release, whereas the G-protein inhibitor, pertussis toxin (1 μg/ml), had an inhibitory effect. The specific lipoxygenase inhibitor, AA-861 (0.1-10 μM), inhibited PAF-activated histamine release, while the leukotriene A₄ hydrolase inhibitor, bestatin (100 μΜ), had only a marginal effect. Finally, the Ca²⁺ channel entry blockers, verapamil (3-30 μΜ) and zinc (1.5-50 μΜ), inhibited PAF- induced histamine release. These results suggest that PAF is a unique secretagogue for human basophils unlike antigen, anti-IgE or univalent stimuli.