Kinetic measurements of the release of prostaglandins from perfused rat lungs |
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Authors: | William G. Anderson M.B. Abou-Donia D.B. Menzel |
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Affiliation: | aDepartments of Physiology and Pharmacology and of Medicine Duke Medical Center Durham, North Carolina 27710, USA |
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Abstract: | 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 PGF2 which was determined by bioassay. A novel method for mixing a stream of inhibitors with the perfusate was used to determine PGF2 in the presence of substrate amounts of arachidonic acid. Using this system the apparent Km for PGF2 production with arachidonic acid as the substrate was found to be 1.90 × 10−4M, while the Ki for aspirin was found to be 2.47 × 10−4M. 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 environmental factors on the release of prostaglandins by the lung. |
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Keywords: | Person to whom correspondence should be addressed. |
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