Skip to main content
SpringerLink
Log in

Pathophysiological Roles of Prostanoid Receptors in the Central Nervous System

  • Chapter
Bioactive Lipid Mediators

  • 1319 Accesses

Abstract

Prostanoids comprising prostaglandins (PGs) and thromboxanes exert diverse actions by acting on their specific receptors. Recently, physiological roles of these receptors have been clarified using knockout mice for each receptor as well as receptor-selective agonists and antagonists. In the central nervous system (CNS), prostanoids have been shown to regulate not only fever, but also neuroinflammation, and to play a role in the pathogenesis of many neurodegenerative diseases. In this report, we review the recent research on the roles and molecular mechanisms of prostanoids and their receptors in the CNS and discuss their possibilities as therapeutic targets.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Tai HH, Ensor CM, Tong M, Zhou H, Yan F (2002) Prostaglandin catabolizing enzymes. Prostaglandins Other Lipid Mediat 68-69:483–493

    Article  CAS  PubMed  Google Scholar 

  2. Sugimoto Y, Narumiya S (2007) Prostaglandin E receptors. J Biol Chem 282:11613–11617

    Article  CAS  PubMed  Google Scholar 

  3. Andersen NH, Eggerman TL, Harker LA, Wilson CH, De B (1980) On the multiplicity of platelet prostaglandin receptors. I. Evaluation of competitive antagonism by aggregometry. Prostaglandins 19:711–735

    Article  CAS  PubMed  Google Scholar 

  4. Gardiner PJ, Collier HO (1980) Specific receptors for prostaglandins in airways. Prostaglandins 19:819–841

    Article  CAS  PubMed  Google Scholar 

  5. Hirata M, Hayashi Y, Ushikubi F, Yokota Y, Kageyama R, Nakanishi S, Narumiya S (1991) Cloning and expression of cDNA for a human thromboxane A2 receptor. Nature 349:617–620

    Article  CAS  PubMed  Google Scholar 

  6. Sugimoto Y, Namba T, Honda A, Hayashi Y, Negishi M, Ichikawa A, Narumiya S (1992) Cloning and expression of a cDNA for mouse prostaglandin E receptor EP3 subtype. J Biol Chem 267:6463–6466

    CAS  PubMed  Google Scholar 

  7. Watabe A, Sugimoto Y, Honda A, Irie A, Namba T, Negishi M, Ito S, Narumiya S, Ichikawa A (1993) Cloning and expression of cDNA for a mouse EP1 subtype of prostaglandin E receptor. J Biol Chem 268:20175–20178

    CAS  PubMed  Google Scholar 

  8. Honda A, Sugimoto Y, Namba T, Watabe A, Irie A, Negishi M, Narumiya S, Ichikawa A (1993) Cloning and expression of a cDNA for mouse prostaglandin E receptor EP2 subtype. J Biol Chem 268:7759–7762

    CAS  PubMed  Google Scholar 

  9. Katsuyama M, Nishigaki N, Sugimoto Y, Morimoto K, Negishi M, Narumiya S, Ichikawa A (1995) The mouse prostaglandin E receptor EP2 subtype: cloning, expression, and northern blot analysis. FEBS Lett 372:151–156

    Article  CAS  PubMed  Google Scholar 

  10. Hirata M, Kakizuka A, Aizawa M, Ushikubi F, Narumiya S (1994) Molecular characterization of a mouse prostaglandin D receptor and functional expression of the cloned gene. Proc Natl Acad Sci U S A 91:11192–11196

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Namba T, Oida H, Sugimoto Y, Kakizuka A, Negishi M, Ichikawa A, Narumiya S (1994) cDNA cloning of a mouse prostacyclin receptor: multiple signaling pathways and expression in thymic medulla. J Biol Chem 269:9986–9992

    CAS  PubMed  Google Scholar 

  12. Sugimoto Y, Hasumoto K, Namba T, Irie A, Katsuyama M, Negishi M, Kakizuka A, Narumiya S, Ichikawa A (1994) Cloning and expression of a cDNA for mouse prostaglandin F receptor. J Biol Chem 269:1356–1360

    CAS  PubMed  Google Scholar 

  13. Hirai H, Tanaka K, Yoshie O, Ogawa K, Kenmotsu K, Takamori Y, Ichimasa M, Sugamura K, Nakamura M, Takano S, Nagata K (2001) Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. J Exp Med 193:255–261

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Tang DG, Grossi IM, Tang KQ, Diglio CA, Honn KV (1995) Inhibition of TPA and 12(S)-HETE-stimulated tumor cell adhesion by prostacyclin and its stable analogs: rationale for their antimetastatic effects. Int J Cancer 60:418–425

    Article  CAS  PubMed  Google Scholar 

  15. Tabata H, Tanaka S, Sugimoto Y, Kanki H, Kaneko S, Ichikawa A (2002) Possible coupling of prostaglandin E receptor EP1 to TRP5 expressed in Xenopus laevis oocytes. Biochem Biophys Res Commun 298:398–402

    Article  CAS  PubMed  Google Scholar 

  16. Ito S, Sakamoto K, Mochizuki-Oda N, Ezashi T, Miwa K, Okuda-Ashitaka E, Shevchenko VI, Kiso Y, Hayaishi O (1993) Prostaglandin F2α receptor is coupled to Gq in cDNA-transfected Chinese hamster ovary cells. Biochem Biophys Res Commun 200:756–762

    Article  Google Scholar 

  17. Dorn GW, Becker MW (1993) Thromboxane A2 stimulated signal transduction in vascular smooth muscle. J Pharmacol Exp Ther 265:447–456

    CAS  PubMed  Google Scholar 

  18. Namba T, Sugimoto Y, Negishi M, Irie A, Ushikubi F, Kakizuka A, Ito S, Ichikawa A, Narumiya S (1993) Alternative splicing of C-terminal tail of prostaglandin E receptor subtype EP3 determines G-protein specificity. Nature 365:166–170

    Article  CAS  PubMed  Google Scholar 

  19. Hatae N, Yamaoka K, Sugimoto Y, Negishi M, Ichikawa A (2002) Augmentation of receptor-mediated adenylyl cyclase activity by Gi-coupled prostaglandin receptor subtype EP3 in a Gβγ subunit-independent manner. Biochem Biophys Res Commun 290:162–168

    Article  CAS  PubMed  Google Scholar 

  20. Yamaoka K, Yano A, Kuroiwa K, Morimoto K, Inazumi T, Hatae N, Tabata H, Segi-Nishida E, Tanaka S, Ichikawa A, Sugimoto Y (2009) Prostaglandin EP3 receptor superactivates adenylyl cyclase via the Gq/PLC/Ca2+ pathway in a lipid raft-dependent manner. Biochem Biophys Res Commun 389:678–682

    Article  CAS  PubMed  Google Scholar 

  21. Buchanan FG, Gorden DL, Matta P, Shi Q, Matrisian LM, DuBois RN (2006) Role of β-arrestin 1 in the metastatic progression of colorectal cancer. Proc Natl Acad Sci U S A 103:1492–1497

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Kluger MJ (1991) Fever: role of pyrogens and cryogens. Physiol Rev 71:93–127

    CAS  PubMed  Google Scholar 

  23. Itami T, Ema M, Kanoh S (1986) Antipyretic mechanism of indomethacin in rabbits. J Pharmacobiodyn 9:271–275

    Article  CAS  PubMed  Google Scholar 

  24. Cao C, Matsumura K, Yamagata K, Watanabe Y (1997) Involvement of cyclooxygenase-2 in LPS-induced fever and regulation of its mRNA by LPS in the rat brain. Am J Physiol 272:R1712–R1725

    CAS  PubMed  Google Scholar 

  25. Sehic E, Székely M, Ungar AL, Oladehin A, Blatteis CM (1996) Hypothalamic prostaglandin E2 during lipopolysaccharide-induced fever in guinea pigs. Brain Res Bull 39:391–399

    Article  CAS  PubMed  Google Scholar 

  26. Saigusa T, Iriki M (1988) Regional differentiation of sympathetic nerve activity during fever caused by intracerebroventricular injection of PGE2. Pflugers Arch 411:121–125

    Article  CAS  PubMed  Google Scholar 

  27. Ushikubi F, Segi E, Sugimoto Y, Murata T, Matsuoka T, Kobayashi T, Hizaki H, Tuboi K, Katsuyama M, Ichikawa A, Tanaka T, Yoshida N, Narumiya S (1998) Impaired febrile response in mice lacking the prostaglandin E receptor subtype EP3. Nature 395:281–284

    Article  CAS  PubMed  Google Scholar 

  28. Sugimoto Y, Shigemoto R, Namba T, Negishi M, Mizuno N, Narumiya S, Ichikawa A (1994) Distribution of the messenger RNA for the prostaglandin E receptor subtype EP3 in the mouse nervous system. Neuroscience 62:919–928

    Article  CAS  PubMed  Google Scholar 

  29. Leibbrandt A, Penninger JM (2008) RANK/RANKL: regulators of immune responses and bone physiology. Ann N Y Acad Sci 1143:123–150

    Article  CAS  PubMed  Google Scholar 

  30. Hanada R, Leibbrandt A, Hanada T, Kitaoka S, Furuyashiki T, Fujihara H, Trichereau J, Paolino M, Qadri F, Plehm R, Klaere S, Komnenovic V, Mimata H, Yoshimatsu H, Takahashi N, von Haeseler A, Bader M, Kilic SS, Ueta Y, Pifl C, Narumiya S, Penninger JM (2009) Central control of fever and female body temperature by RANKL/RANK. Nature 462:505–509

    Article  CAS  PubMed  Google Scholar 

  31. Nakamura K, Kaneko T, Yamashita Y, Hasegawa H, Katoh H, Ichikawa A, Negishi M (1999) Immunocytochemical localization of prostaglandin EP3 receptor in the rat hypothalamus. Neurosci Lett 260:117–120

    Article  CAS  PubMed  Google Scholar 

  32. Nakamura K, Matsumura K, Kaneko T, Kobayashi S, Katoh H, Negishi M (2002) The rostral raphe pallidus nucleus mediates pyrogenic transmission from the preoptic area. J Neurosci 22:4600–4610

    CAS  PubMed  Google Scholar 

  33. Tsuchiya H, Oka T, Nakamura K, Ichikawa A, Saper CB, Sugimoto Y (2008) Prostaglandin E2 attenuates preoptic expression of GABAA receptors via EP3 receptors. J Biol Chem 283:11064–11071

    Article  CAS  PubMed  Google Scholar 

  34. Kataoka N, Hioki H, Kaneko T, Nakamura K (2014) Psychological stress activates a dorsomedial hypothalamus-medullary raphe circuit driving brown adipose tissue thermogenesis and hyperthermia. Cell Metab 20:346–358

    Article  CAS  PubMed  Google Scholar 

  35. Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, Knapp DJ, Crews FT (2007) Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 55:453–462

    Article  PubMed Central  PubMed  Google Scholar 

  36. Lehnardt S (2010) Innate immunity and neuroinflammation in the CNS: the role of microglia in Toll-like receptor-mediated neuronal injury. Glia 58:253–263

    PubMed  Google Scholar 

  37. Montine TJ, Milatovic D, Gupta RC, Valyi-Nagy T, Morrow JD, Breyer RM (2002) Neuronal oxidative damage from activated innate immunity is EP2 receptor-dependent. J Neurochem 83:463–470

    Article  CAS  PubMed  Google Scholar 

  38. Shie FS, Montine KS, Breyer RM, Montine TJ (2005) Microglial EP2 is critical to neurotoxicity from activated cerebral innate immunity. Glia 52:70–77

    Article  PubMed  Google Scholar 

  39. Shi J, Johansson J, Woodling NS, Wang Q, Montine TJ, Andreasson K (2010) The prostaglandin E2 E-prostanoid 4 receptor exerts anti-inflammatory effects in brain innate immunity. J Immunol 184:7207–7218

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Chun KS, Lao HC, Trempus CS, Okada M, Langenbach R (2009) The prostaglandin receptor EP2 activates multiple signaling pathways and β-arrestin1 complex formation during mouse skin papilloma development. Carcinogenesis 30:1620–1627

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Murakami M, Kudo I (2002) Phospholipase A2. J Biochem 131:285–292

    Article  CAS  PubMed  Google Scholar 

  42. Rosenberger TA, Villacreses NE, Contreras MA, Bonventre JV, Rapoport SI (2003) Brain lipid metabolism in the cPLA2 knockout mouse. J Lipid Res 44:109–117

    Article  CAS  PubMed  Google Scholar 

  43. Nomura DK, Morrison BE, Blankman JL, Long JZ, Kinsey SG, Marcondes MC, Ward AM, Hahn YK, Lichtman AH, Conti B, Cravatt BF (2011) Endocannabinoid hydrolysis generates brain prostaglandins that promote neuroinflammation. Science 334:809–813

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH (2010) Mechanisms underlying inflammation in neurodegeneration. Cell 140:918–934

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Teismann P, Tieu K, Choi DK, Wu DC, Naini A, Hunot S, Vila M, Jackson-Lewis V, Przedborski S (2003) Cyclooxygenase-2 is instrumental in Parkinson’s disease neurodegeneration. Proc Natl Acad Sci U S A 100:5473–5478

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. McKee AC, Carreras I, Hossain L, Ryu H, Klein WL, Oddo S, LaFerla FM, Jenkins BG, Kowall NW, Dedeoglu A (2008) Ibuprofen reduces Aβ, hyperphosphorylated tau and memory deficits in Alzheimer mice. Brain Res 1207:225–236

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Piro JR, Benjamin DI, Duerr JM, Pi Y, Gonzales C, Wood KM, Schwartz JW, Nomura DK, Samad TA (2012) A dysregulated endocannabinoid-eicosanoid network supports pathogenesis in a mouse model of Alzheimer’s disease. Cell Rep 1:617–623

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Professors Kazuhisa Nakayama, Atsushi Ichikawa, and Shuh Narumiya for precious advice. We also thank Dr. Soken Tsuchiya, Ms. Toshiko Sugimoto, and Ms. Yue Kanagawa for their continuous support. We are grateful to Dr. H. Akiko Popiel for careful reading of the manuscript.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi, Kumamoto, 862-0973, Japan

    Tomoaki Inazumi & Yukihiko Sugimoto

  2. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama, 332-0012, Japan

    Tomoaki Inazumi & Yukihiko Sugimoto

Authors
  1. Tomoaki Inazumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yukihiko Sugimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yukihiko Sugimoto .

Editor information

Editors and Affiliations

  1. Department of Biochemistry, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Takehiko Yokomizo

  2. Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

    Makoto Murakami

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Japan

About this chapter

Cite this chapter

Inazumi, T., Sugimoto, Y. (2015). Pathophysiological Roles of Prostanoid Receptors in the Central Nervous System. In: Yokomizo, T., Murakami, M. (eds) Bioactive Lipid Mediators. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55669-5_4

Download citation

Publish with us

Policies and ethics

Search

Navigation