Albumin-eicosanoid interactions. A model system to determine their attributes and inhibition.
A model system was developed to (a) reflect the chemical attributes of the microenvironment involved in albumin-eicosanoid interactions and (b) determine the effects of other ligands on these interactions. Albumin-dependent modulation of prostaglandin stability was chosen as the basis for this system. 15-Ketoprostaglandin E2 (PGE2) was evaluated as a model ligand because under special conditions it decomposes with formation of a visible chromophore. Human serum albumin, in a concentration-dependent fashion, catalyzed the dehydration of 15-keto-PGE2 with the concurrent generation of this chromophore (lambda max = 505 nm, epsilon = 35,000). Since chromophore production from 15-keto-PGE2 in albumin-free solution occurs only at pH greater than 10, the results suggest that albumin-eicosanoid interactions involve a microenvironment with alkaline attributes. The effect of other ligands on albumin-15-keto-prostaglandin E2 interactions was determined by monitoring their ability to inhibit the spectral component of these interactions. Inhibition correlated with an affinity for specific binding sites on albumin. At mole ratios of ligand/albumin below 1, only phenylbutazone, its analogs, and warfarin inhibited chromophore development. Other ligands including fatty acids, steroids, tryptophan, and drugs with an affinity for other binding sites were ineffective inhibitors.
D000527:Alprostadil / Q000031:analogs & derivatives*; D000818:Animals; D002417:Cattle; D004285:Dogs; D004355:Drug Stability; D006736:Horses; D006801:Humans; D007700:Kinetics; D010215:Papio; D011458:Prostaglandins E / Q000378:metabolism*; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013552:Swine
D011458:Prostaglandins E; D012709:Serum Albumin; C011008:15-ketoprostaglandin E; D012710:Serum Albumin, Bovine; D000527:Alprostadil