Targeted gene disruption of the prostaglandin e2 ep2 receptor

  • Richard M. Breyer
  • Christopher R. J. Kennedy
  • Yahua Zhang
  • Youfei Guan
  • Matthew D. Breyer
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 507)


Prostaglandins comprise a diverse family of autacoids derived from cyclooxygenase (COX) metabolism of arachidonic acid to PGG/H2, leading to the generation of five principal bio-active prostaglandin (PG) metabolites: PGE2, PGF2a, PGD2, PGI2, and TXA2 1. The PGs play a role in a broad range of physiologic activities including modulating inflammation, ovulation and arterial blood pressure. These PG metabolites exert their effects at least in part by interacting with distinct G-protein coupled receptors (GPCRs) 2, each with distinct ligand selectivity and signal transduction pathways.


Mean Arterial Pressure Selective Agonist Prostanoid Receptor Target Gene Disruption Null Animal 
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  1. 1.
    Smith, W. Prostanoid biosynthesis and mechanisms of action. Am. J. Physiol. 263, F181–191 (1992).Google Scholar
  2. 2.
    Toh, H., Ichikawa, A. & Narumiya, S. Molecular evolution of receptors for eicosanoids. FEBS Letters 361, 17–21 (1995).PubMedCrossRefGoogle Scholar
  3. 3.
    Coleman, R.A., Kennedy, I., Humphrey, P.P.A., Bunce, K. & Lumley, P. Prostanoids and their Receptors. in Comprehensive Medicinal Chemistry, Vol. 3 (ed. Emmet, J.C.) 643–714 (Pergammon Press, Oxford, 1990).Google Scholar
  4. 4.
    Coleman, R.A., Smith, W.L. & Narumiya, S. VIII. International union of pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes. Pharmacol. Rev. 46, 205–229 (1994).Google Scholar
  5. 5.
    Narumiya, S., Sugimoto, Y. & Ushikubi, F. Prostanoid Receptors: Structures, Properties, and Functions. Physiol Rev 79, 1193–1226 (1999).PubMedGoogle Scholar
  6. 6.
    Schlondorff, D. Renal complications of nonsteroidal anti-inflammatory drugs. Kidney /nt. 44, 643–653 (1993).CrossRefGoogle Scholar
  7. 7.
    Jackson, E. Relationship between renin release and blood pressure response to nonsteroidal anti-inflammatory drugs in hypertension. Hypertension 14, 469–471 (1989).PubMedCrossRefGoogle Scholar
  8. 8.
    Coleman, R.A., Kennedy, I., Humphrey, P.P.A., Bunce, K. & Lumley, P. Prostanoids and their receptors. in Comprehensive Medical Chemistry, Vol. 3 (ed. Emmer, J.C.) 643–714 (Oxford: Pergammon Press, 1990).Google Scholar
  9. 9.
    Coleman, R.A., Kennedy, I. & Sheldrick, R.L.G. New Evidence with Selective Agonists and Antagonists for the Subclassification of PGE2 -sensitive (EP) Receptors. Adv. in Prostaglandin, Thromboxane, and Leukotriene Res. 17, 467–470 (1987).Google Scholar
  10. 10.
    Challis, J.R.G. Prostaglandins and reproduction-what do knockouts really tell us? Nature Med. 3, 1326–1327 (1997).PubMedCrossRefGoogle Scholar
  11. 11.
    Priddy, A.R. & Killick, S.R. Eicosanoids and ovulation. Prostaglandins, Leukotrienes and Essential Fatty acids 49, 827–831 (1993).CrossRefGoogle Scholar
  12. 12.
    Weitlauf, H.M. Biology of implantation. in: The physiology of reproduction, (Raven Press, New York, 1994).Google Scholar
  13. 13.
    Bonventre, J.V. et al. Reduced fertility and postischaemic brain injury in mice deficient in cytosolic phospholipase A2. Nature 390, 622–625 (1997).PubMedCrossRefGoogle Scholar
  14. 14.
    Uozumi, N. et al. Role of cytosolic phospholipase A2 in allergic response and parturition. Nature 390, 618–622 (1997).PubMedCrossRefGoogle Scholar
  15. 15.
    Lau, I.F., Saksena, S.K. & Chang, M.C. Pregancy blockade by indomethacin, an inhibitor of prostaglandin synthesis: its reversal by prostaglandins and progesterone in mice. Prostaglandins 4, 795–803 (1973).PubMedCrossRefGoogle Scholar
  16. 16.
    Lim, H., Paria, B. C., Das, S. K., Dinchuk, J. E., Langenbach, R., Trzaskos, J. M., and Dey, S. K. Multiple female reproductive failures in cyclooxygenase 2-deficient mice. Cell 91, 197–208 (1997).PubMedCrossRefGoogle Scholar
  17. 17.
    Smith, G., Roberts, R., Hall, C. & Nuki, G. Reversible ovulatory failure associated with the development of luteinized unruptured follicles in women with inflammatory arthritis taking non-steroidal anti-inflammatory drugs. Br. J. Rheumatol. 35, 458–462 (1996).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Richard M. Breyer
    • 1
    • 2
  • Christopher R. J. Kennedy
    • 1
  • Yahua Zhang
    • 1
  • Youfei Guan
    • 1
  • Matthew D. Breyer
    • 1
    • 3
    • 4
  1. 1.Departments of Medicine (Division of Nephrology)Vanderbilt University Division of NephrologyNashvilleUSA
  2. 2.PharmacologyVanderbilt University Division of NephrologyNashvilleUSA
  3. 3.Molecular Physiology and BiophysicsVanderbilt University Division of NephrologyNashvilleUSA
  4. 4.Veterans Administration Medical Center, and Vanderbilt University School of MedicineVanderbilt University Division of NephrologyNashvilleUSA

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