Potentiation of leukotriene formation in pulmonary and vascular tissue.
Leukotriene (LT) release from vascular and pulmonary tissue was assessed by a radioimmunoassay for peptide leukotrienes (i.e., LTC4, LTD4 and LTE4). The calcium ionophore A-23187 at 1-3 micrograms/ml and platelet activating factor (PAF) at 10 micrograms/ml produced marked formation of peptide leukotrienes in minced cat pulmonary tissue. This was also confirmed by bioassay of the incubates in isolated perfused cat coronary arteries. Rat pulmonary tissue was comparable to cat with regard to LT production, but guinea-pig lung produced about 30-50% less on a weight basis. In addition, aortic and coronary artery vessel walls produced significant amounts of LTs. The time course for maximal leukotriene production occurred at 45-60 min of incubation at 37 degrees C in both the radioimmunoassay and the bioassay. Cat coronary artery constricted markedly to LTC4 or LTD4 (30-40 mm Hg) and to the lung or blood vessel incubate. This constriction was virtually totally blocked by the leukotriene antagonist FPL-55712, but not by the thromboxane receptor antagonist, pinane thromboxane A2, the alpha-adrenergic receptor antagonist, phenoxybenzamine, or the angiotensin receptor antagonist, saralasin. Thus, pulmonary and vascular tissue produce leukotrienes that appear to exert coronary constrictor effects on specific leukotriene receptors. These results indicate that the ischemia of shock and anaphylaxis may be accentuated by the release of peptide leukotrienes.
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002415:Cats; D006168:Guinea Pigs; D066298:In Vitro Techniques; D017999:Leukotriene E4; D008168:Lung / Q000378:metabolism*; D008469:Meclofenamic Acid / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D051381:Rats; D013189:SRS-A / Q000031:analogs & derivatives* / Q000096:biosynthesis*; D013997:Time Factors
D010972:Platelet Activating Factor; D013189:SRS-A; D000001:Calcimycin; D008469:Meclofenamic Acid; D017999:Leukotriene E4