Platelet-activating factor-induced contraction of guinea-pig lung parenchymal strips: possible involvement of arachidonate metabolites.
The identification of the mediators possibly involved in platelet-activating factor (PAF)-induced contraction of guinea-pig lung parenchymal strips (GPLP) was attempted by means of antagonists and inhibitors. Histamine, serotonin, acetylcholine (ACh) or other transmitters released from the nerve terminals are not likely to play a role in this response, since specific antagonists and tetrodotoxin did not affect the contraction. PAF antagonists (brotizolam and WEB 2086) produced a concentration-dependent inhibition of the contraction. Inhibitors of TXA2 synthesis (dazoxiben) and of 5-lipoxygenase (nordihydroguaiaretic acid and AA 861) and antagonists of TXA2 (ICI 159995) and peptidoleukotrienes (L 649923 and LY 171883, but not FPL 55712) produced a significant inhibition of the PAF-induced response at concentrations which did not reduce the ACh-induced response. These results suggest that arachidonate metabolites, both of the cyclo-oxygenase and of the lipoxygenase pathway, are determinants of the PAF-induced contraction of GPLP.
Del Monte
M
M
Department of Pharmacology, Laboratori Guidotti SpA, Pisa, Italy.
Subissi
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000502:physiology*; D001285:Atropine / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D006168:Guinea Pigs; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors; D008168:Lung / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles
D001095:Arachidonic Acids; D001381:Azepines; D016861:Cyclooxygenase Inhibitors; D006993:Hypnotics and Sedatives; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D014227:Triazines; D014230:Triazoles; C052518:WEB 2086; D013928:Thromboxane A2; C020960:brotizolam; D001285:Atropine; D000109:Acetylcholine