Structural requirements for, and the effects of chemicals on, the rat pulmonary inactivation of prostaglandins.
We have investigated the removal of prostaglandins (PGs) from the pulmonary circulation using the isolated perfused rat lung in order to determine which parts of the PG molecule were essential for transport into the pulmonary tissue. From these studies we propse that three functional groups of the PG molecule are necessary for transport into the lung tissue: the carboxylic acid group at carbon 1, hydroxyl group at carbon 15, and an oxygen group at carbon 11. The geometrical relationship between these groups is important for transport since reduction of the 13, 14-double bond reduced transport, and changing the C-15 hydroxyl from an S to R configuration abolished transport. Various chemicals, drugs, and PG antagonists were tested for their ability to inhibit the transport system resposible for PG removal from the circulation. Diphloretin phosphate and polyphloretin phosphate were effective inhibitors, whereas dexamethasone, bromocresol green N-ethyl maleimide and imipramine were moderately effective inhibitors. The PG antagonist, SC-19220, 7-oxo-13-prostynoic acid, and hydrocortisone were ineffective.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D008168:Lung / Q000378:metabolism*; D008297:Male; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D011454:Prostaglandins A / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism; D011465:Prostaglandins, Synthetic / Q000378:metabolism* / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats
D000893:Anti-Inflammatory Agents; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011454:Prostaglandins A; D011458:Prostaglandins E; D011460:Prostaglandins F; D011465:Prostaglandins, Synthetic