Decreased arachidonic acid liberation participates in the anti-aggregatoryeffect of the histamine H-1-receptor antagonist Bromadryl

The in vitro effect of the histamine H-1-receptor antagonist Bromadryl on a ggregation of human blood platelets was studied, Bromadryl inhibited stimul ated platelet aggregation in a dose-dependent may. Depending on the aggrega tion stimulus used, its mean inhibitory concentrations were 16 mu mol/litre (thrombin), 18 mu mol/litre (A23187), 92 mu mol/litre (adrenaline) and 395 mu mol/litre (adenosine diphosphate). The inhibitory effect was most prono unced in aggregation stimulated with phorbol 12-myristate 13-acetate (IC50 = 3 mu mol/litre), suggesting interference of Bromadryl with protein kinase C activity. In Bromadryl-treated platelets, a very good correlation was fo und 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 Brom adryl with phospholipase A(2) (an enzyme liberating arachidonic acid) may b e involved in the anti-aggregatory effect, However, in platelets stimulated with thrombin, thromboxane formation was decreased at a lower mean inhibit ory concentration of Bromadryl (6 mu mol/litre) than arachidonic acid liber ation (72 mu mol/litre); thus, phospholipase A(2) does not seem to be the o nly site in the arachidonate metabolism cascade affected by Bromadryl, Alth ough specific interference of Bromadryl with histamine receptors could not be excluded, alterations in platelet membrane structure and functions are s upposed to be principal in the anti-aggregatory effect of Bromadryl.