Advertisement

Heart and Vessels

, Volume 25, Issue 5, pp 432–437 | Cite as

Dopamine receptor subtypes in the native human heart

  • Carlo Cavallotti
  • Massimo Mancone
  • Paolo Bruzzone
  • Maurizio SabbatiniEmail author
  • Fiorenzo Mignini
Original Article

Abstract

The present study first time detected D1–D5 dopamine receptor subtypes in the native human heart simultaneously, found presence of D1, D2, D4, and D5 in cardiac tissues, and revealed distribution features of dopamine receptor subtypes in the epicardium, myocardium, and endocardium. Samples from four native hearts coming from young brain-dead donors, which for technical reason were not used for transplants, were studied. Dopamine receptors were revealed by immunochemistry technique and immunoblot analysis. Morphometrical quantification of the density of each receptor subtype was performed by an image analyzer. Our results demonstrate that only four subtypes of dopamine receptors can be found in cardiac tissues: D1, D2, D4, and D5. These dopamine receptors have been detected in endocardium, myocardium, and epicardium. D1 receptors were stored primarily in the epicardial layer. Dopamine receptors are distributed in the wall of both atria and ventricles, and its transmural gradient can be described in the wall of the human heart. Sections of atria and ventricles exposed to antidopamine receptor antibodies showed fluorescent-positive reaction in the epicardium, myocardium and endocardium. D4 receptor immune reactivity was remarkably less intense than D2 receptor immune reactivity. All the subtypes of dopamine receptors are in close relationships with all cardiac structures. Our findings provide a favorable basis for researching the role of dopamine receptors in controlling functions of the human heart and in the pathogenesis of cardiovascular diseases.

Key words

Myocardium Ventricles Atrium Dopamine receptor subtypes 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Goldberg LI (1972) Cardiovascular and renal actions of dopamine: potential clinical applications. Pharmacol Rev 24:1–29PubMedGoogle Scholar
  2. 2.
    Moreira-Rodrigues M, Sampaio-Maia B, Pestana M (2009) Renal dopaminergic system activity in rat remnant kidney up to twenty-six weeks after surgery. Life Sci 84:409–416CrossRefPubMedGoogle Scholar
  3. 3.
    Sherlock M, Toogood AA, Steeds R (2009) Dopamine agonist therapy for hyperprolactinaemia and cardiac valve dysfunction; a lot done but much more to do. Heart 95:522–523CrossRefPubMedGoogle Scholar
  4. 4.
    Gildea JJ (2009) Dopamine and angiotensin as renal counterregulatory systems controlling sodium balance. Curr Opin Nephrol Hypertens 18:28–32CrossRefPubMedGoogle Scholar
  5. 5.
    Yamamoto T, Shirayama T, Takahashi T, Matsubara H (2009) Altered expression of Na+ transporters at the mRNA level in rat normal and hypertrophic myocardium. Heart Vessels 24:54–62CrossRefPubMedGoogle Scholar
  6. 6.
    Sibley DR, Monsma F Jr (1992) Molecular biology of dopamine receptors. Trends Pharmacol Sci 13:61–69CrossRefPubMedGoogle Scholar
  7. 7.
    Gingrich JA, Caron MG (1993) Recent advances in the molecular biology of dopamine receptors. Annu Rev Neurosci 16:299–321CrossRefPubMedGoogle Scholar
  8. 8.
    Hilfiker-Kleiner D, Sliwa K, Drexler H (2008) Peripartum cardiomyopathy: recent insights in its pathophysiology. Trends Cardiovasc Med 18:173–179CrossRefPubMedGoogle Scholar
  9. 9.
    Jin XH, Zhang JZ, Zhao YI, Zhao RR (1997) Localization of dopamine 1a receptor mRNA in different vascular beds in rat: a no-radioactive in situ hybridisation study. Methods Find Exp Clin Pharmacol 19:657–663PubMedGoogle Scholar
  10. 10.
    Goldberg LI, Kohli JD (1979) Peripheral pre-and post synaptic dopamine receptors: are they different from dopamine receptors in the central nervous system? Commun Psychopharmacol 3:447–456PubMedGoogle Scholar
  11. 11.
    Ozono R, O’Connell DP, Vaughan C, Botkin-Walk SF, Felder RA, Carey RM (1996) Expression of the subtype 1a dopamine receptor in the rat heart. Hypertension 27:693–703PubMedGoogle Scholar
  12. 12.
    Remme WJ (2001) Dopaminergic agents in heart failure: rebirth of an old concept. Cardiovasc Drugs Ther 15:107–109CrossRefPubMedGoogle Scholar
  13. 13.
    Murphy M (2000) Dopamine: a role in the pathogenesis and treatment of hypertension. J Hum Hypertens 14suppl 1:s47–s50CrossRefPubMedGoogle Scholar
  14. 14.
    Cavallotti C, Nuti F, Bruzzone P, Mancone M (2002) Age-related changes in dopamine D2 receptors in rat heart and coronary vessels. Clin Exp Pharmacol Physiol 29:412–418CrossRefPubMedGoogle Scholar
  15. 15.
    Mazzi V (1977) Manuale di tecniche istologiche ed istochimiche. Ed. Piccin, Padua, p 486Google Scholar
  16. 16.
    Lowry OH, Rosebrough NJ, Farr AL, Randall JJ (1951) Protein measurement with the folin phenol reagent. Biol Chem 193: 265–275Google Scholar
  17. 17.
    Microsystems Imaging Solutions (1997) Manual of Quantimet methods. UK Edition. Microsystems Imaging Solutions, CambridgeGoogle Scholar
  18. 18.
    Castino M, Roletto E (1992) Statistica applicata. Edizioni Piccin, PadovaGoogle Scholar
  19. 19.
    Li HZ, Han LP, Jiang CM, Li H, Zhao YJ, Gao J, Lin Y, Ma SX, Tian Y, Yang BF, Xu CQ (2008) Effect of dopamine receptor 1 on apoptosis of cultured neonatal rat cardiomyocytes in simulated ischaemia/reperfusion. Basic Clin Pharmacol Toxicol 102:329–336CrossRefPubMedGoogle Scholar
  20. 20.
    Moens AL, Claeys MJ, Timmermans JP, Vrints CJ (2005) Myocardial ischemia/reperfusion injury, a clinical view on a complex pathophysiological process. Int J Cardiol 100:179–190CrossRefPubMedGoogle Scholar
  21. 21.
    Gerö D, Módis K, Nagy N, Szoleczky P, Tóth ZD, Dormán G, Szabó C (2007) Oxidant-induced cardiomyocyte injury: identification of the cytoprotective effect of a dopamine 1 receptor agonist using a cell-based high-throughput assay. Int J Mol Med 20:749–761PubMedGoogle Scholar
  22. 22.
    Zeng C, Han Y, Huang H, Yu C, Ren H, Shi W, He D, Huang L, Yang C, Wang X, Zhou L, Jose PA (2009) D1-like receptors inhibit insulin-induced vascular smooth muscle cell proliferation via down-regulation of insulin receptor expression. J Hypertens 27: 1033–1041CrossRefPubMedGoogle Scholar
  23. 23.
    Jose PA, Eisner GM, Felder RA (2000) Renal dopamine and sodium homeostasis. Curr Hypertens Rep 2:174–183CrossRefPubMedGoogle Scholar
  24. 24.
    Banday AA, Lokhandwala MF (2008) Dopamine receptors and hypertension. Curr Hypertens Rep 10:268–275CrossRefPubMedGoogle Scholar
  25. 25.
    Dal Toso R, Sommer B, Ewert M, Herb A, Pritchett DB, Bach A, Shivers BD, Seeburg PH (1989) The dopamine D2 receptor: two molecular forms generated by alternative splicing. EMBO J 20:4025–4034Google Scholar
  26. 26.
    Giros B, Sokoloff P, Martres MP, Riou JF, Emorine LJ, Schwartz JC (1989) Alternative splicing directs the expression of two D2 dopamine receptor isoforms. Nature 342:923–926CrossRefPubMedGoogle Scholar
  27. 27.
    Monsma FJ Jr, McVittie LD, Gerfen CR, Mahan LC, Sibley DR (1989) Multiple D2 dopamine receptors produced by alternative RNA splicing. Nature 342:926–929CrossRefPubMedGoogle Scholar
  28. 28.
    Wolfe SE, Morris SJ (1999) Dopamine D2 receptor isoforms expressed in AtT20 cells differentially couple to G proteins to acutely inhibit high voltage-activated calcium channels. J Neurochem 73:2375–2382CrossRefPubMedGoogle Scholar
  29. 29.
    Takeuchi Y, Fukunaga K (2003) Differential subcellular localization of two dopamine D2 receptor isoforms in transfected NG108-15 cells. J Neurochem 85:1064–1074CrossRefPubMedGoogle Scholar
  30. 30.
    Shin SY, Lee JH, Min B, Lee YH (2006) The translation inhibitor anisomycin induces Elk-1-mediated transcriptional activation of egr-1 through multiple mitogen-activated protein kinase pathways. Exp Mol Med 38:677–685PubMedGoogle Scholar
  31. 31.
    Wang JC, Zhao Y, Wang CX, Liu W, Shao JH (2008) Myocardial expression and distribution of calcineurin in normal and failing human ventricular myocardium. Zhonghua Xin Xue Guan Bing Za Zhi 36:332–336PubMedGoogle Scholar
  32. 32.
    Bai CG, Liu XH, Liu WQ, Ma DL (2008) Regional expression of the hypoxia-inducible factor (HIF) system and association with cardiomyocyte cell cycle re-entry after myocardial infarction in rats. Heart Vessels 23:193–200CrossRefPubMedGoogle Scholar

Copyright information

© Springer Japan 2010

Authors and Affiliations

  • Carlo Cavallotti
    • 1
  • Massimo Mancone
    • 1
  • Paolo Bruzzone
    • 2
  • Maurizio Sabbatini
    • 3
    Email author
  • Fiorenzo Mignini
    • 4
  1. 1.Department of Cardiovascular and Respiratory Science, Section of Human AnatomyUniversity of Rome “La Sapienza”RomeItaly
  2. 2.Department of Surgery and Organ TransplantUniversity of Rome “La Sapienza”RomeItaly
  3. 3.Department of Clinical and Experimental Medicine, Laboratory of Human AnatomyUniversity of Eastern Piedmont “A. Avogadro”NovaraItaly
  4. 4.Department of Experimental Medicine and Public HealthUniversity of CamerinoCamerinoItaly

Personalised recommendations