The effects of antiallergic and bronchodilator drugs on platelet-activating factor (PAF-acether) induced bronchospasm and platelet aggregation.
Platelet activating factor (PAF-acether) is a potential mediator of asthma and inflammation. Recently, the suggestion was made that inhibition of PAF-acether by disodium cromoglycate (DSCG) might be partly responsible for the effectiveness of DSCG in asthma. We have extended these studies and examined the effects of antiallergic and bronchodilator drugs on PAF-acether induced bronchospasm after i.v. administration in guinea pigs and in vitro platelet aggregation in rabbits. Neither DSCG nor Wy-41,195, a potent orally effective antiallergic, altered either of the PAF-acether responses. Furthermore, aerosolized ipratropium, promethazine, ketotifen and FPL 55712 failed to affect the PAF-acether-induced bronchospasm. The same drugs were also ineffective against platelet aggregation induced by PAF-acether. In contrast, aerosolized thiazinamium chloride inhibited the bronchospasm and also inhibited PAF-acether-induced platelet aggregation. Thiazinamium chloride possessed weak antiaggregatory effects against ADP and was without effect against arachidonic acid-induced platelet aggregation. Both lipoxygenase and cyclooxygenase products of arachidonic acid metabolism appear to be involved in PAF-acether bronchospasm since i.v. administered lipoxygenase inhibitors (phenidone, BW755c and NDGA) and indomethacin independently inhibited this in vivo response. However, these drugs failed to alter platelet aggregation to PAF-acether. Thiazinamium chloride may be capable of directly antagonizing the PAF-acether-induced platelet aggregatory response and, in addition, inhibiting the synthesis and/or effects of bronchoconstrictor amines and endogenously generated arachidonic acid metabolites.
D000818:Animals; D001986:Bronchial Spasm / Q000139:chemically induced / Q000517:prevention & control*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002867:Chromones / Q000494:pharmacology; D004205:Cromolyn Sodium / Q000494:pharmacology; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D008297:Male; D010972:Platelet Activating Factor / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011398:Promethazine / Q000494:pharmacology; D011817:Rabbits
D001993:Bronchodilator Agents; D002867:Chromones; D006634:Histamine H1 Antagonists; D010972:Platelet Activating Factor; C006312:FPL 55712; D011398:Promethazine; D004205:Cromolyn Sodium