Spasmogenic properties of platelet-activating factor: evidence for a direct mechanism in the contractile response of pulmonary tissues.
Platelet-activating factor (1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine; PAF) induces a specific, dose-dependent contraction of guinea pig lung parenchymal strips with an ED50 value of 10(-9) M. The smooth muscle contractile activity of PAF in this system was not effected by the H1-blocking antihistamine, pyrilamine (10(-6) M), the prostaglandin synthesis inhibitors, indomethacin (10(-5) M), aspirin (10(-4) M), or sulfinpyrazone (5 X 10(-4) M), the leukotriene synthesis inhibitor, nordihydroguaiaretic acid (NDGA; 10(-5) M), the leukotriene antagonist FPL 55712 (10(-6) M) or the inhibitor of arachidonic acid metabolism, eicosatetraynoic acid (ETYA; 2 X 10(-5) M). The role of platelets in this system was also investigated. PAF-mediated contractions were not attenuated following platelet depletion using nitrogen mustard, nor were they augmented by the addition of exogenous platelets. Furthermore, isolated platelets incubated with PAF did not release stable substances spasmogenic for lung parenchymal strips. Finally, contractile activity of PAF was demonstrated in lung parenchymal strips from rats, a species whose platelets are insensitive to PAF at elevated concentrations. Taken together, these data show that PAF contracts smooth muscle of guinea pig lung parenchyma independently of endogenous histamine, arachidonic acid metabolites, or platelets trapped within the pulmonary vasculature. It is concluded, therefore, that PAF may act directly on contractile cells of the lung.
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology; D002396:Catechols / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung; D009637:Masoprocol; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010972:Platelet Activating Factor / Q000502:physiology*; D051381:Rats; D013442:Sulfinpyrazone / Q000494:pharmacology; D013929:Thromboxane B2 / Q000032:analysis
D002396:Catechols; D002867:Chromones; D010972:Platelet Activating Factor; D015117:5,8,11,14-Eicosatetraynoic Acid; D013929:Thromboxane B2; D009637:Masoprocol; C006312:FPL 55712; D001241:Aspirin; D013442:Sulfinpyrazone; D007213:Indomethacin