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, 84 (1), 256-60

(5Z,13E)-(15S)-9 alpha,11 beta,15-trihydroxyprosta-5,13-dien-1-oic Acid (9 alpha,11 Beta-Prostaglandin F2): Formation and Metabolism by Human Lung and Contractile Effects on Human Bronchial Smooth Muscle

(5Z,13E)-(15S)-9 alpha,11 beta,15-trihydroxyprosta-5,13-dien-1-oic Acid (9 alpha,11 Beta-Prostaglandin F2): Formation and Metabolism by Human Lung and Contractile Effects on Human Bronchial Smooth Muscle

K Seibert et al. Proc Natl Acad Sci U S A.

Abstract

Prostaglandin D2 (PGD2) was recently found to be stereospecifically converted to the compound (5Z,13E)-(15S)-9 alpha,11 beta,15-trihydroxyprosta-5,13-dien-1-oic acid (9 alpha,11 beta-PGF2) by a human liver cytosolic NADPH-dependent 11-ketoreductase enzyme. Because PGD2 is a potent bronchoconstrictor and is released into bronchoalveolar lavage fluid after allergen stimulation in patients with allergic asthma, the ability of human lung to metabolize PGD2 to 9 alpha,11 beta-PGF2 and the contractile effects of 9 alpha,11 beta-PGF2 on human bronchial smooth muscle were investigated. The 100,000 X g supernatant of human lung converted PGD2 in the presence of an NADPH-generating system stereospecifically to 9 alpha,11 beta-PGF2 at a rate of 3.46 +/- 0.94 pmol per min per mg of protein. 9 alpha,11 beta-PGF2 was found to contract human bronchial rings in a dose-dependent fashion with a potency virtually identical with that of both PGD2 and PGF2 alpha, known potent bronchial constrictors. PGD2 was found to be a very poor substrate for human lung 15-hydroxyprostaglandin dehydrogenases and to be preferentially metabolized by lung to 9 alpha,11 beta-PGF2. 9 alpha,11 beta-PGF2 was also found to be a very poor substrate for the lung 15-hydroxyprostaglandin dehydrogenases. Thus, once formed, 9 alpha,11 beta-PGF2 would not be expected to be rapidly inactivated in situ by these metabolic enzymes. These results suggest that 9 alpha,11 beta-PGF2 may participate along with other putative mediators in the pulmonary allergic response in humans.

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References

    1. FEBS Lett. 1976 Sep 15;68(1):59-62 - PubMed
    1. Anal Biochem. 1976 May 7;72:248-54 - PubMed
    1. Biochim Biophys Acta. 1979 Nov 21;575(2):185-92 - PubMed
    1. J Biol Chem. 1980 Mar 10;255(5):1779-82 - PubMed
    1. Prostaglandins. 1985 Sep;30(3):383-400 - PubMed

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