Decreased arachidonic acid liberation participates in the anti-aggregatory effect of the histamine H(1)-receptor antagonist Bromadryl.

The in vitro effect of the histamine H(1)-receptor antagonist Bromadryl on aggregation of human blood platelets was studied. Bromadryl inhibited stimulated platelet aggregation in a dose-dependent way. Depending on the aggregation stimulus used, its mean inhibitory concentrations were 16 micromol/litre (thrombin), 18 micro mol/litre (A23187), 92 micromol/litre (adrenaline) and 395 micromol/litre (adenosine diphosphate). The inhibitory effect was most pronounced in aggregation stimulated with phorbol 12-myristate 13-acetate (IC(50) = 3 micromol/litre), suggesting interference of Bromadryl with protein kinase C activity. In Bromadryl-treated platelets, a very good correlation was found between aggregation and liberation of arachidonic acid; the correlation coefficients calculated for thrombin- and A23187-stimulated platelets were 0.94123 and 0.98611, respectively. This indicates that interaction of Bromadryl with phospholipase A(2) (an enzyme liberating arachidonic acid) may be involved in the anti-aggregatory effect. However, in platelets stimulated with thrombin, thromboxane formation was decreased at a lower mean inhibitory concentration of Bromadryl (6 micromol/litre) than arachidonic acid liberation (72 micromol/litre); thus, phospholipase A(2) does not seem to be the only site in the arachidonate metabolism cascade affected by Bromadryl. Although specific interference of Bromadryl with histamine receptors could not be excluded, alterations in platelet membrane structure and functions are supposed to be principal in the anti-aggregatory effect of Bromadryl.