Cyclooxygenase products and cyclic nucleotide levels with infusion of arachidonic acid, PGI2, PGE2, PGF2, and 6-keto-PGF1 in an isolated dog lung.
Arachidonic acid (AA) was infused into the pulmonary artery of an isolated dog lung perfused with a physiologic salt solution. This led to elevations in pulmonary cyclic AMP and prostaglandins (PGs) including PGE2, PGF2 alpha, TXB2 (a metabolite of TXA2), and 6-keto-PGF1 alpha (a metabolite of PGI2). The elevations were prevented by PG synthesis inhibitors. A dose of PGI2 comparable to that produced from AA led to elevations in cyclic AMP. These elevations were not reduced by PG synthesis inhibitors; this indicated that the inhibitors did not reduce cyclic AMP except by inhibiting metabolism of AA. The PGE2 led to lesser elevations in cyclic AMP than did PGI2; PGF2 alpha and 6-keto-PGF1 alpha did not increase cyclic AMP. Levels of cyclic AMP were not elevated. We conclude that some of the elevation in cyclic AMP from AA was most likely from production of PGs since elevations in both were prevented by the inhibitors. However, the possibility remains that AA metabolites other than PGs also contributed to elevations in cyclic AMP. We also conclude that PGI2 most likely accounted for some of the cyclic AMP elevation from AA since PGI2 could be readily produced in amounts that elevate cyclic AMP. However, the possibility remains that PGE2, the less consistent cyclic AMP stimulators (l.e., PGF2 alpha and 6-keto-PGF1 alpha), TXA2 or TXB2, or PGs not measured in this study also contributed to the elevations in cyclic AMP from AA.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D004285:Dogs; D011464:Epoprostenol / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D011448:Prostaglandin Antagonists / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism
D001095:Arachidonic Acids; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D000242:Cyclic AMP