Kinetic measurements of the release of prostaglandins from perfused rat lungs.
Prostaglandins released from isolated ventilated and perfused rat lungs were measured by a simple modification of the Vane technique using the rat stomach fundus as a continuous bioassay tissue. Exogenously supplied arachidonic acid was converted mainly to PGF2alpha which was determined by bioassay. A novel method for mixing a stream of inhibitors with the perfusate was used to determine PGF2alpha in the presence of substrate amounts of arachidonic acid. Using this system the apparent Km for PGF2alpha production with arachidonic acid as the substrate was found to be 1.90 X 10(-4)M, while the Ki for aspirin was found to 2.47 X 10(-4)M. These kinetic parameters are close to those reported for cell free systems and subcellular fractions suggesting that both substrate and inhibitor have ready access to the site of prostaglandin synthesis. The method appears to be generally useful to determine the effect of drugs and environment factors on the release of prostaglandins by the lung.
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D010477:Perfusion; D011453:Prostaglandins / Q000096:biosynthesis; D011460:Prostaglandins F / Q000378:metabolism*; D051381:Rats; D013270:Stomach / Q000187:drug effects
D001095:Arachidonic Acids; D011453:Prostaglandins; D011460:Prostaglandins F