Involvement of endoperoxides and thromboxanes in anaphylactic reactions.
Our recent work on prostaglandin endoperoxides in the lung has shown that: 1. The endoperoxides were 5 to 10 times more potent than PGF2alpha in an in vitro preparation of respiratory smooth muscle, i.e., the guinea pig trachea. 2. The endoperoxides were 5 to 10 times more potent than PGF2alpha in causing an increase in tracheal insufflation pressure in the anaesthetized, artificially ventilated guinea pig. 3. Endoperoxides formed from exogenous arachidonic acid in homogenates of guinea pig lung and in intact guinea pig lung were converted to a large extent into metabolites different from the classical prostaglandins, i.e., thromboxane B2 (8-(1-hydroxy-3-oxopropyl)-9-12L-dihydroxy-5,10-heptadecadienoic acid) and HHT (12L-hydroxy-5,8,10-heptadecatrienoic acid). 4. Injection of antigen into sensitized guinea pig lungs caused a significant release of the endoperoxide metabolite, thromboxane B2. PGF2alpha has previously been implicated to be involved in anaphylaxis (14). The findings described above show that the prostaglandin endoperoxides are important not only as precursors of PGF2alpha but also through their own effects on airway smooth muscle. Furthermore, the release of thromboxane B2 indicates that its immediate precursor, the biologically active thromboxane A2 is also formed in this system (15). This compound, which has a half-life of 30 to 40 sec causes platelet aggregation and contraction of the isolated rabbit aorta (15). Work is in progress to study the respiratory effects of thromboxane A2 and its possible role in anaphylactic reactions.
D000707:Anaphylaxis / Q000378:metabolism*; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002474:Cell-Free System; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005849:Gerbillinae; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006880:Hydroxy Acids / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010545:Peroxides / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism / Q000494:pharmacology; D011714:Pyrans / Q000378:metabolism; D011817:Rabbits; D051381:Rats
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D006880:Hydroxy Acids; D010545:Peroxides; D011453:Prostaglandins; D011714:Pyrans