Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

Expression of functional prostaglandin D (DP) receptors in human corpus cavernosum smooth muscle

Abstract

Prostaglandin D2 (PGD2) binds to specific G-protein coupled receptors (DP) and induces smooth muscle relaxation by stimulating the synthesis of intracellular cAMP. In this study, we examined the role of PGD2 and DP receptors in regulating human penile smooth muscle contractility. We determined that human corpus cavernosum tissue and smooth muscle cells in culture expressed functional DP receptor and lipocalin-like prostaglandin D synthase by reverse-transcribed polymerase chain reaction (RT-PCR). Functional PGD synthase activity was confirmed by the synthesis of PGD2 in human corpus cavernosum smooth muscle cells upon addition of exogenous arachidonic acid. Organ bath preparations of human corpus cavernosum tissue strips, contracted with phenylephrine, relaxed in a dose-dependent fashion to either PGD2 or the DP selective agonist BW245C. Cultures of human corpus cavernosum smooth muscle cells treated with BW245C showed a two-fold increase in cAMP synthesis. These data are consistent with the expression of functional DP receptors in human corpus cavernosum. This suggests the presence of an intact prostanoid autocrine system that may play a role in regulating penile erectile function.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Pierce KL, Gil DW, Woodward DF, Regan JW . Cloning of human prostanoid receptors Trends Pharm Sci 1995; 16: 1–22.

    Article  Google Scholar 

  2. Narumiya S, Sugimoto Y, Ushikubi F . Prostanoid receptors: structures, properties, and functions Physiol Rev 1999; 79: 1193–1226.

    Article  CAS  Google Scholar 

  3. Andersson KE . Pharmacology of penile erection Pharmacol Rev 2001; 53: 417–450.

    CAS  Google Scholar 

  4. Nehra A, Barrett DM, Moreland RB . Pharmacotherapeutic advances in the treatment of erectile dysfunction Mayo Clin Proc 1999; 74: 709–715.

    Article  CAS  Google Scholar 

  5. Boie Y et al. Molecular cloning and characterization of the human prostanoid DP receptor J Biol Chem 1995; 270: 18910–18916.

    Article  CAS  Google Scholar 

  6. Kanaoka Y et al. Cloning and crystal structure of hematopoietic prostaglandin D synthase Cell 1997; 90: 1085–1095.

    Article  CAS  Google Scholar 

  7. Urade Y, Hayaishi O . Prostaglandin D2 and sleep regulation Biochim Biophys Acta 1999; 1436: 606–615.

    Article  CAS  Google Scholar 

  8. Okuda-Ashitaka E et al. Cyclic-AMP-dependent Ca2+ influx elicited by prostaglandin D2 in freshly isolated nonchromaffin cells from bovine adrenal medulla Biochim Biophys Acta 1993; 1176: 148–154.

    Article  CAS  Google Scholar 

  9. Nagata A et al. Human brain prostaglandin D synthase has been evolutionarily differentiated from lipophilic-ligand carrier proteins Proc Natl Acad Sci USA 1991; 88: 4020–4024.

    Article  CAS  Google Scholar 

  10. Roy AC, Tan SM, Kottegoda SR, Ratnam SS . Ability of human corpus cavenosum to generate prostaglandins and thromboxanes in vitro IRCS Med Sci 1984; 12: 608.

    CAS  Google Scholar 

  11. Daley JT et al. Prostanoid production in rabbit corpus cavernosum I. Regulation by oxygen tension J Urol 1996; 155: 1482–1487.

    Article  CAS  Google Scholar 

  12. Moreland RB et al. Oxygen-dependent prostanoid synthesis activates functional PGE receptors on human corpus caver-nosum smooth muscle cells Am J Physiol 2001; 281: H552–H557.

    CAS  Google Scholar 

  13. Hedlund H, Andersson KE . Contraction and relaxation induced by some prostanoids in isolated human penile erectile tissue and cavernous artery J Urol 1985; 134: 1245–1250.

    Article  CAS  Google Scholar 

  14. Palmer LS et al. Characterization of cyclic AMP accumulation in cultured human corpus cavernosum smooth muscle cells J Urol 1994; 152: 1308–1314.

    Article  CAS  Google Scholar 

  15. Moreland RB et al. Misoprostol induces relaxation of human corpus cavernosum smooth muscle: Comparison to prostaglandin E1 Int J Impotence Res 2000; 12: 107–110.

    Article  CAS  Google Scholar 

  16. Traish AM et al. G-protein-coupled receptor agonists augment adenylyl cyclase activity induced by forskolin in human corpus cavernosum smooth muscle cells Receptors and Signal Transduction 1997; 7: 123–134.

    Google Scholar 

  17. Moreland RB et al. PGE1 suppresses the induction of collagen synthesis by transforming growth factor-β1 in human corpus cavernosum smooth muscle J Urol 1995; 153: 826–834.

    Article  CAS  Google Scholar 

  18. Edelstein RA et al. A rapid and simple method for the detection of prostate specific antigen mRNA in archival tissue specimens using a reverse transcription-polymerase chain reaction assay Urology 1995; 45: 597–603.

    Article  CAS  Google Scholar 

  19. Watkins MT et al. Immediate responses of endothelial cells to hypoxia and reoxygenation: an in vitro model of cellular dysfunction Am J Physiol 1995; 268: H749–H756.

    CAS  PubMed  Google Scholar 

  20. Kim N et al. Oxygen tension regulates the nitric oxide pathway. Physiological role in penile erection J Clin Invest 1993; 91: 437–442.

    Article  CAS  Google Scholar 

  21. Gerashchenko D et al. Dominant expression of rat prostanoid DP receptor mRNA in leptomeninges inner segments of photoreceptor cells, iris epithelium, and ciliary processes J Neurochem 1998; 71: 937–945.

    Article  CAS  Google Scholar 

  22. Tokugawa Y et al. Lipocalin-type prostaglandin D synthase in human male reproductive organs and seminal plasma Biol Reprod 1998; 58: 600–607.

    Article  CAS  Google Scholar 

  23. Beasley RC et al. Effect of a thromboxane receptor antagonist on PGD2- and allergen-induced bronchoconstriction J Appl Physiol 1989; 66: 1685–1693.

    Article  CAS  Google Scholar 

  24. Crider JY, Griffen BW, Sharif NA . Prostaglandin DP receptors positively coupled to adenylyl cyclase in embryonic bovine tracheal (EBTr) cells: pharmacological characterization using agonists and antagonists Br J Pharmacol 1999; 127: 204–210.

    Article  CAS  Google Scholar 

  25. Kiriyama M et al. Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells Br J Pharmacol 1997; 122: 217–224.

    Article  CAS  Google Scholar 

  26. Giles H et al. The classification of prostaglandin DP-receptors in platelets and vasculature using BW A868C, a novel, selective and potent competitive antagonist Br J Pharmacol 1989; 96: 291–300.

    Article  CAS  Google Scholar 

  27. Matsugi T et al. Selective prostaglandin D2 receptor stimulation elicits ocular hypotensive effects in rabbits and cats Eur J Pharmacol 1995; 275: 245–250.

    Article  CAS  Google Scholar 

  28. Imoto Y et al. Alpha-subunit of Gs directly activates cardiac calcium channels in lipid bilayers Am J Physiol 1988; 255: H722–H728.

    CAS  PubMed  Google Scholar 

  29. Yu HJ, Ma H, Green RD . Calcium entry via L-type calcium channels acts as a negative regulator of adenylyl cyclase activity and cyclic AMP levels in cardiac myocytes Mol Pharmacol 1993; 4: 689–693.

    Google Scholar 

  30. Lader AS et al. Cardiac Gs alpha overexpression enhances L-type calcium channels through an adenylyl cyclase independent pathway Proc Natl Acad Sci USA 1998; 95: 9669–9674.

    Article  CAS  Google Scholar 

  31. Hayaishi O . Molecular mechanisms of sleep-wake regulation: roles of prostaglandins D2 and E2 FASEB J 1991; 5: 2575–2581.

    Article  CAS  Google Scholar 

  32. Mizoguchi A et al. Dominant localization of prostaglandin D receptors on arachnoid trabecular cells in mouse basal forebrain and their involvement in the regulation of non-rapid eye movement sleep Proc Natl Acad Sci USA 2001; 98: 11674–11679.

    Article  CAS  Google Scholar 

  33. Moreland RB . Is there a role of hypoxema in penile fibrosis? Int J Impot Res 1998; 10: 113–120.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the excellent technical assistance of Cynthia Gallant, Sandra Kwak and Erika Liné as well as the administrative assistance of Jerie McGrath-Cerqua. This work was supported by grants R29-DK47950, R01-DK39080, R01-DK40025 and K01-DK02696 from the National Institutes of Health and a grant from the General Research Service of the Veterans Administration (MTW).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R B Moreland.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Moreland, R., Nehra, A., Kim, N. et al. Expression of functional prostaglandin D (DP) receptors in human corpus cavernosum smooth muscle. Int J Impot Res 14, 446–452 (2002). https://doi.org/10.1038/sj.ijir.3900900

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijir.3900900

Keywords

This article is cited by

Search

Quick links