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Coronary Arterial Prostacyclin Synthetase and Prostaglandin E2 Isomerase Activities

  • Dennis B. McNamara
  • Alice Z. Landry
  • Philip J. Kadowitz
  • Morris D. Kerstein
  • John L. Hussey
  • Robert S. Rosenson
  • Howard L. Lippton
  • Albert L. Hyman
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

Prostaglandin E2 (PGE2) isomerase and prostacyclin (PGI2) synthetase are the major endoperoxide (PGH2)-metabolizing enzymes present in microsomes isolated from vascular tissue. The PGE2 isomerase activity specifically requires the addition of GSH (Ogino et al., 1977). Prostacyclin has potent vasodilator and platelet antiag-gregatory activity (Vane, 1983). Therefore, modulation of PGI2 synthetase activity is of prime physiological importance in the regulation of blood vessel function. Reducing agents such as GSH have been reported to augment prostaglandin production by protecting the cyclooxygenase enzyme system (arachidonic acid→ PGH2) from self-catalyzed deactivation (Egan et al, 1976). However, little evidence exists for the effects of these agents on augmenting prostacyclin synthetase activity (McNamara et al.1984). We report the concentration-dependent modulation of the formation of 6-keto-PGF, the stable breakdown product of PGI2, by GSH and dithiothreitol (DTT) and unmasking of PGE2 isomerase in microsomes isolated from bovine coronary artery.

Keywords

Microsomal Protein Isomerase Activity Prostaglandin Endoperoxide Human Saphenous Vein Incubation Volume 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Beetens, J. R., Claeys, M., and Herman, A. G., 1983, Vitamin C increases the formation of prostacyclin by aortic rings from various species and neutralizes the inhibitory effect of the 15-hydroxy-arach-idonic acid, Br. J. Pharmacol. 80:249–254.PubMedCrossRefGoogle Scholar
  2. Bunting, S., Moncada, S., and Vane, J.R., 1983, The prostacyclin-thromboxane A2 balance: Patho-physiological and therapeutic implications, Br. Med. Bull. 39:271–276.PubMedGoogle Scholar
  3. Carrier, R., Cragoe, E.J., Ethier, D., Ford-Hutchinson, A.W., Girard, Y., Hall, R.A., Hamel, P., Rokach, J., Share, N.N., Stone, C.A., and Yusko, P., 1984, Studies on L-640,035: A novel antagonist of contractile prostanoids in the lung, Br. J. Pharmacol. 82:389–395.PubMedCrossRefGoogle Scholar
  4. Carstein, M.E., and Miller, J.D., 1977, Effects of prostaglandins and oxytocin on calcium release from a uterine microsomal fraction, J. Biol. Chem. 252:1576–1581.Google Scholar
  5. Egan, R.W., Paxton, J., and Kuehl, F.A., Jr., 1976, Mechanism for irreversible self-deactivation of prostaglandin synthetase, J. Biol. Chem. 251:7329–7335.PubMedGoogle Scholar
  6. Fantone, J.C, and Kinnes, D.A., 1983, Prostaglandin E1 and prostaglandin I2 modulation of Superoxide production by human neutrophils, Biochem. Biophys. Res. Commun. 113:506–512.PubMedCrossRefGoogle Scholar
  7. Farooqui, M.Y.H., and Ahmed, A., 1984, Circadian periodicity of tissue glutathione and its relationship with lipid peroxidation in rats, Life Sci. 34:2413–2418.PubMedCrossRefGoogle Scholar
  8. Gerritsen, M.E., and Printz, M.P., 1981, Sites of prostaglandin synthesis in the bovine heart and isolated bovine coronary microvessels, Circ. Res. 49:1152–1163.PubMedCrossRefGoogle Scholar
  9. Greenberg, S., 1981, Effect of prostacyclin and 9,11-epoxymethanoprostaglandin H2 on calcium and magnesium fluxes and tension development in canine intralobar pulmonary arteries and veins, J. Pharmacol. Exp. Ther. 219:326–337.PubMedGoogle Scholar
  10. Hyman, A.L., Kadowitz, P.J., Lands, W.E.M., Crawford, C.G., Fried, J., and Barton, J., 1978, Coronary vasodilator activity of 13,14-dehydroprostacyclin methyl ester: Comparison with prostacyclin and other prostanoids, Proc. Natl. Acad. Sci. U.S.A. 75:3522–3526.PubMedCrossRefGoogle Scholar
  11. Kerstein, M.D., Saroyan, M., McMullen-Laird, M., Hyman, A.L., Kadowitz, P.J., and McNamara, D.B., 1983, Metabolism of prostaglandins in human saphenous vein, J. Surg. Res. 35:91–100.PubMedCrossRefGoogle Scholar
  12. Lefer, A.M., Ogletree, M.S., Smith, J.B., Silver, M.J., Nicolaou, K.C, and Gasic, G.P., 1978, Prostacyclin: A potentially valuable agent for preserving myocardial tissue in acute myocardial infarction, Science 200:52–54.PubMedCrossRefGoogle Scholar
  13. Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.S., 1951, Protein measurement with folin phenol reagent, J. Biol. Chem. 193:265–275.PubMedGoogle Scholar
  14. McMullen-Laird, M., McNamara, D. B., Kerstein, M. D., Hyman, A. L., and Kadowitz, P. J., 1982, Human lung metabolism of prostaglandin endoperoxide, Circulation 66(11): 166.Google Scholar
  15. McNamara, D.B., Roulet, M.J., Gruetter, C.A., Hyman, A.L., and Kadowitz, P.J., 1980, Correlation of prostaglandin-induced mitochondrial calcium release with contraction in bovine intrapulmonary vein, Prostaglandins 20:311–320.PubMedCrossRefGoogle Scholar
  16. McNamara, D.B., Hussey, J.L., Kerstein, M.D., Rosenson, R.J., Hyman, A.L., and Kadowitz, P.J., 1984, Modulation of prostacyclin synthetase and unmasking of PGE2 isomerase in bovine coronary arterial microsomes, Biochem. Biophys. Res. Commun. 118:33–39.PubMedCrossRefGoogle Scholar
  17. Meister, A., and Anderson, M. E., 1983, Glutathione, Annu. Rev. Biochem. 52:711–760.PubMedCrossRefGoogle Scholar
  18. Needleman, P., 1976, Organic nitrate metabolism, Annu. Rev. Pharmacol. 16:81–93.CrossRefGoogle Scholar
  19. Ogino, N., Miyamoto, T., Yamamoto, S., and Hayaishi, O., 1977, Prostaglandin endoperoxide E isomerase from bovine vesicular gland microsomes, a glutathione requiring enzyme, J. Biol. Chem. 252:890–895.PubMedGoogle Scholar
  20. Okuma, M., Takayma, H., and Uchino, H., 1980, Generation of prostacyclin-like substance and lipid peroxidation in vitamin E-deficient rats, Prostaglandins 19:527–536.PubMedCrossRefGoogle Scholar
  21. Romson, J.L., Hook, B.G., Rigot, V.H., Schork, M.A., Swanson, D.P., and Lucchesi, B.R., 1982, The effect of ibuprofen on accumulation of Indium-lll-labeled platelets and leukocytes in experimental myocardial infarction, Circulation 66:1002–1011.PubMedCrossRefGoogle Scholar
  22. Schror, K., Grodzinska, L., and Darius, H., 1981, Stimulation of coronary vascular prostacyclin and inhibition of human platelet thromboxane A2 after low dose nitroglycerin, Thromb. Res. 23:59–67.PubMedCrossRefGoogle Scholar
  23. She, H.S., McNamara, D.B., Spannhake, E.W., Hyman, A.L., and Kadowitz, P.J., 1981, Metabolism of prostaglandin endoperoxide by microsomes from cat lung, Prostaglandins 21:531–541.PubMedCrossRefGoogle Scholar
  24. Thomas, G., Skrinska, V., Lucas, F., and Butkus, A., 1984, Platelet glutathione and thromboxane synthesis in diabetes mellitus, Fed. Proc. 43:1040.Google Scholar
  25. Vane, J. R., 1983, Adventures and excursions in bioassay: The stepping stones to prostacyclin, Br. J. Pharmacol. 79:821–838.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • Dennis B. McNamara
    • 1
  • Alice Z. Landry
    • 1
  • Philip J. Kadowitz
    • 1
  • Morris D. Kerstein
    • 2
  • John L. Hussey
    • 2
  • Robert S. Rosenson
    • 3
  • Howard L. Lippton
    • 2
  • Albert L. Hyman
    • 3
  1. 1.Department of PharmacologyTulane University School of MedicineNew OrleansUSA
  2. 2.Department of SurgeryTulane University School of MedicineNew OrleansUSA
  3. 3.Department of MedicineTulane University School of MedicineNew OrleansUSA

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