Bronchoconstriction induced by N-formyl-methionyl-leucyl-phenylalanine in the guinea pig; involvement of arachidonic acid metabolites.
The chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (F-met-leu-phe) was shown to be a potent myotropic agent on the guinea-pig parenchymal strip (IC50, 2 X 10(-7)M). The response was unaffected by the histamine (H1) antagonist, mepyramine, but in the presence of the cyclooxygenase inhibitor, indomethacin, the dose response curve was shifted to the left (IC50, 4 X 10(-8)M) and the maximal response reduced. Injection of F-met-leu-phe into perfused guinea pig lungs resulted in the release of leukotriene-like activity which was detected by superfusion over guinea-pig ileum preparations in the presence and absence of FPL-55712. Intravenous injection of F-met-leu-phe to spontaneously breathing anaesthetized guinea pigs resulted in transient increases in pulmonary resistance and blood pressure and decreases in dynamic compliance and heart rate. The pulmonary parameters were significantly inhibited by BW 755C, indomethacin, FPL-55712 and a contractile prostanoid antagonist, L-640,035. These results demonstrate that F-met-leu-phe is a potent bronchoconstrictor in the guinea pig and that the peptide may induce these changes through the generation of products of the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000008:administration & dosage / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013189:SRS-A / Q000378:metabolism; D013997:Time Factors
D001095:Arachidonic Acids; D002867:Chromones; D013189:SRS-A; D016718:Arachidonic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; C006312:FPL 55712; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin