Skip to main content

Advertisement

SpringerLink
Log in

The Role of Receptor Transactivation in the Cardioprotective Effects of Preconditioning and Postconditioning

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

Abstract

Analysis of published data indicates that activation of adenosine, opioid, bradykinin, calcitonin gene-related peptide (CGRP), and epidermal growth factor (EGF) receptors plays an important trigger role in ischemic preconditioning. Cannabinoids imitate the infarct-limiting effect of preconditioning. Endogenous adenosine, opioids, bradykinin, and CGRP are involved in the infarct-limiting effects of ischemic postconditioning. Cannabinoids also imitate the cardioprotective effect of postconditioning. Recent studies have supported the occurrence of heterodimerization of G-protein-coupled receptors (GPC receptors) and transactivation of EGF receptors by GPC receptors. Intracellular interaction of δ1 opioid receptors and adenosine A1 receptors is important for cardioprotection. Furthermore, evidence has been obtained for the involvement of transactivation of EGF receptors by a multitude of GPC receptors, including adenosine, acetylcholine, bradykinin, and opioid receptors. These data support the occurrence of convergent pathways in which multiple GPC receptors can interact (or function independently) and transactivate EGF receptor-dependent kinase signaling to provide cytoprotection.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. A. V. Krylatov, N. A. Bernatskaya, L. N. Maslov, et al., “Increases in the resistance of the heart to arrhythmogenic influences and decreases in myocardial ischemic necrosis zones on activation of cannabinoid receptors,” Ros. Fiziol. Zh., 88, No. 5, 560–567 (2002).

    CAS  Google Scholar 

  2. O. V. Lasukova, L. N. Maslov, S. Yu. Ermakov, et al., “The role of cannabinoid receptors in the regulation of the tolerance of the heart to ischemia and reperfusion,” Izv. Ros. Akad. Nauk. Ser. Biol., 35, No. 4, 471–478 (2008).

    Google Scholar 

  3. Yu. B. Lishmanov, L. N. Maslov, S. V. Tam, and A. A. Bogomaz, “The opioid system and the resistance of the heart to damage in ischemia-reperfusion,” Ros. Fiziol. Zh., 86, No. 2, 164–173 (2000).

    CAS  Google Scholar 

  4. Yu. B. Lishmanov and L. N. Maslov, “Ischemic postconditioning of the heart. Receptor mechanisms and the potential for clinical application,” Kardiologiya, 50, No. 6, 68–74 (2010).

    PubMed  Google Scholar 

  5. Yu. B. Lishmanov, L. N. Maslov, I. G. Khaliulin, et al., “The role of heat shock proteins, aldose reductase, Bcl-2 protein, and microRNA in the mechanism of delayed preconditioning of the heart,” Ros. Fiziol. Zh., 96, No. 5, 472–487 (2010).

    CAS  Google Scholar 

  6. Yu. B. Lishmanov, L. N. Maslovб T. Krieg, and I. G. Khaliulin, “The problem of the final effector of late ischemic preconditioning of the heart,” Ros. Fiziol. Zh., 96, No. 4, 337–352 (2010).

    Google Scholar 

  7. L. N. Maslov, O. V. Lasukova, A. V. Krylatov, et al., “Changes in inotropic heart function and the extent of damage to cardiomyocytes on activation of cannabinoid receptors in conditions of ischemia and reperfusion,” Ros. Fiziol. Zh., 89, No. 9, 1108–1106 (2003).

    CAS  Google Scholar 

  8. L. N. Maslov, Yu. B. Lishmanov, and N. V. Solenkova, “Adaptation of the myocardium to ischemia. The first phase of ischemic preconditioning,” Usp. Fiziol. Nauk., 37, No. 3, 25–41 (2006).

    PubMed  CAS  Google Scholar 

  9. L. N. Maslov, T. Krieg, and B. Daivan, “Postconditioning – a universal protective phenomenon,” Patol. Fiziol. Ter., 3, 2–6 (2009).

    Google Scholar 

  10. L. N. Maslov, “New approaches to the prophylaxis and treatment of ischemic and reperfusional damage to the heart in acute myocardial infarction,” Sib. Med. Zh. (Tomsk), 25, No. 2, 17–24 (2010).

    Google Scholar 

  11. L. N. Maslov,Yu. B. Lishmanov, I. G. Khaliulin, et al., “Uncoupling proteins and their role in regulating the resistance of the brain and heart to the effects of ischemia and reperfusion,” Ros. Fiziol. Zh., 97, No. 8, 761–780 (2011).

    CAS  Google Scholar 

  12. D. S. Ugdyzhekova, A. V. Krylatov, N. A. Bernatskaya, et al., “Potential for limiting the zone of myocardial ischemic necrosis by activating cannabinoid receptors,” Byull. Eksperim. Biol. Med., 133, No. 2, 148–150 (2002).

    Article  Google Scholar 

  13. I. G. Khaliulin, L. N. Maslov,Yu. K. Podoksenov, and Yu. B. Lishmanov, “Signal mechanisms of the cardioprotective effect of hypothermic preconditioning,” Ros. Fiziol. Zh., 97, No. 6, 624–631 (2011).

    CAS  Google Scholar 

  14. J. Boonstra, P. Rijken, B. Humbel, et al., “The epidermal growth factor,” Cell Biol. Int., 19, No. 5, 413–430 (1995).

    Article  PubMed  CAS  Google Scholar 

  15. J. S. Brugge and R. L. Erikson, “Identification of a transformation-specific antigen induced by an avian sarcoma virus,” Nature, 269, No. 5626, 346–348 (1977).

    Article  PubMed  CAS  Google Scholar 

  16. Z. Cao, L. Liu, and D. M. Van Winkle, “Met5-enkephalin-induced cardioprotection occurs via transactivation of EGFR and activation of PI3K,” Am. J. Physiol. Heart Circ. Physiol., 288, No. 4, H1955–H1964 (2005).

    Article  PubMed  CAS  Google Scholar 

  17. W. Chai, S. Mehrotra, A. H. Jan Dander, and R. G. Schoemaker, “The role of calcitonin gene-related peptide (CGRP) in ischemic postconditioning in isolated rat hearts,” Eur. J. Pharmacol., 531, No. 1–3, 246–253 (2006).

    Article  PubMed  CAS  Google Scholar 

  18. G. L. Chien, K. Mohtadi, R. A. Wolff, and D. M. Van Winkle, “Naloxone blockade of ischemic preconditioning does not require central nervous system participation,” Basic Res. Cardiol., 94, 136–143 (1999).

    Article  PubMed  CAS  Google Scholar 

  19. M. V. Cohen, X. M. Yang, G. S. Liu, et al., “Acetylcholine, bradykinin, opioids, and phenylephrine, but not adenosine, trigger preconditioning by generating free radicals and opening mitochondrial KATP channels,” Circ. Res., 89, No. 3, 273–278 (2001).

    Article  PubMed  CAS  Google Scholar 

  20. M. V. Cohen, S. Philipp, T. Krieg, et al., “Preconditioning-mimetics bradykinin and DADLE activate PI3-kinase through divergent pathways,” J. Mol. Cell. Cardiol., 42, No. 4, 842–851 (2007).

    Article  PubMed  CAS  Google Scholar 

  21. G. D. Dalton, C. E. Bass, C. G. Van Horn, and A. C. Howlett, “Signal transduction via cannabinoid receptors,” CNS Neurol. Disord. Drug Targets, 8, No. 6, 422–431 (2009).

    Article  PubMed  CAS  Google Scholar 

  22. N. Defer, J. Wan, R. Souktani, and B. Escoubet, “The cannabinoid receptor type 2 promotes cardiac myocyte and fibroblast survival and protects against ischemia/reperfusion-induced cardiomyopathy,” FASEB J., 23, No. 7, 2120–2130 (2009).

    Article  PubMed  CAS  Google Scholar 

  23. J. M. Downey and M. V. Cohen, “Signal transduction in ischemic preconditioning,” Adv. Exp. Med. Biol., 430, 39–55 (1997).

    Article  PubMed  CAS  Google Scholar 

  24. J. M. Downey, A. M. Davis, and M. V. Cohen, “Signaling pathways in ischemic preconditioning,” Heart Fail. Rev., 12, No. 3–4, 181–188 (2007).

    Article  PubMed  CAS  Google Scholar 

  25. N. Dzimiri, “Receptor crosstalk. Implications for cardiac function, disease and therapy,” Eur. J. Biochem., 269, No. 19, 4713–4730 (2002).

    Article  PubMed  CAS  Google Scholar 

  26. W. Eckhart, M. A. Hutchinson, and T. Hunter, “An activity phosphorylating tyrosine in polyoma T antigen immunoprecipitates,” Cell, 18, No. 4, 925–933 (1979).

    Article  PubMed  CAS  Google Scholar 

  27. K. Forster, A. Kuno, N. Solenkova, et al., “The δ-opioid receptor agonist DADLE at reperfusion protects the heart through activation of pro-survival kinases via EGF receptor transactivation,” Am. J. Physiol. Heart Circ. Physiol., 293, No. 3, H1604–H1608 (2007).

    Article  PubMed  Google Scholar 

  28. M. Goto, Y. Liu, X. M. Yang, et al., “Role of bradykinin in protection of ischemic preconditioning in rabbit hearts,” Circ. Res., 77, No. 3, 611–621 (1995).

    Article  PubMed  CAS  Google Scholar 

  29. E. R. Gross, A. K. Hsu, and G. J. Gross, “GSK3β inhibition and KATP channel opening mediate acute opioid-induced cardioprotection at reperfusion,” Basic Res. Cardiol., 102, No. 4, 341–349 (2007).

    Article  PubMed  CAS  Google Scholar 

  30. M. E. Halkos, F. Kerendi, J. S. Corvera, et al., “Myocardial protection with postconditioning is not enhanced by ischemic preconditioning,” Ann. Thorac. Surg., 78, No. 3, 961–969 (2004).

    Article  PubMed  Google Scholar 

  31. R. S. Herbst, “Review of epidermal growth factor receptor biology,” Int. J. Radiat. Oncol. Biol. Phys., 59, No. 2, Supplement, 21–26 (2004).

  32. M. Hojo, Y. Sudo, Y. Ando, et al., “μ-Opioid receptor forms a functional heterodimer with cannabinoid CB1 receptor: electrophysiological and FRET assay analysis,” J. Pharmacol. Sci., 108, No. 3, 308–319 (2008).

    Article  PubMed  CAS  Google Scholar 

  33. Y. Jang, J. Xi, H. Wang, et al., “Postconditioning prevents reperfusion injury by activating δ-opioid receptors,” Anesthesiology, 108, No. 2, 243–250 (2008).

    Article  PubMed  CAS  Google Scholar 

  34. H. Kin, A. J. Zatta, R. Jiang, et al., “Activation of opioid receptors mediates the infarct size reduction by postconditioning,” J. Mol. Cell. Cardiol., 38, No. 5, 827 (2005).

    Google Scholar 

  35. H. Kin, A. J. Zatta, M. T. Lofye, et al., “Postconditioning reduces infarct size via adenosine receptor activation by endogenous adenosine,” Cardiovasc. Res., 67, No. 1, 124–133 (2005).

    Article  PubMed  CAS  Google Scholar 

  36. T. Krieg, Q. Qin, E. C. McIntosh, et al., “ACh and adenosine activate PI3 kinase in rabbit hearts through transactivation of receptor tyrosine kinases,” Am. J. Physiol. Heart Circ. Physiol., 283, No. 6, H2322–H2330 (2002).

    PubMed  CAS  Google Scholar 

  37. T. Krieg, L. Cui, Q. Qin, et al., “Mitochondrial ROS generation following acetylcholine-induced EGF receptor transactivation requires metalloproteinase cleavage of proHB-EGF,” J. Mol. Cell. Cardiol., 36, No. 3, 435–443 (2004).

    Article  PubMed  CAS  Google Scholar 

  38. A. I. Kuzmin, A. V. Gourine, A. I. Molosh, et al., “Effects of preconditioning on myocardial intestinal levels of ATP and its catabolites during regional ischemia and reperfusion in rat,” Basic Res. Cardiol., 95, No. 2, 127–136 (2000).

    Article  PubMed  CAS  Google Scholar 

  39. R. D. Lasley, P. J. Konyn, J. O. Hegge, and R. M. Mentzer, “Effects of ischemic and adenosine preconditioning on interstitial fluid adenosine and myocardial infarct size,” Am. J. Physiol., 38, No. 4, H1460–H1666 (1995).

    Google Scholar 

  40. P. Y. Law, L. J. Erickson-Hebrandson, Q. Q. Zha, et al., “Heterodimerization of μ- and δ-opioid receptors occurs at the cell surface only and requires receptor-G protein interactions,” J. Biol. Chem., 280, No. 12, 11152–11164 (2005).

    Article  PubMed  CAS  Google Scholar 

  41. D. Li, N. S. Li, Q. Q. Chen, et al., “Calcitonin gene-related peptidemediated cardioprotection of postconditioning in isolated rat hearts,” Regul. Pept., 147, No. 1–3, 4–8 (2008).

    Article  PubMed  CAS  Google Scholar 

  42. G. S. Liu, J. Thornton, D. M. Van Winkle, et al., “Protection against infarction afforded by preconditioning is mediated by A1 adenosine receptors in rabbit heart,” Circulation, 84, No. 1, 350–356 (1991).

    Article  PubMed  CAS  Google Scholar 

  43. J. Lu, W. J. Zang, X. J. Yu, et al., “Effects of postconditioning of adenosine and acetylcholine on the ischemic isolated rat ventricular myocytes,” Eur. J. Pharmacol., 549, No. 1–3, 133–139 (2006).

    Article  PubMed  CAS  Google Scholar 

  44. R. Maggio, G. Aloisi, E. Silvano, et al., “Heterodimerization of dopamine receptors: new insights into functional and therapeutic significance,” Parkinson. Relat. Disord., 15, Suppl. 4, S2–S7 (2009).

    Article  Google Scholar 

  45. G. S. Martin, “The hunting of the Src,” Nat. Rev. Mol. Cell. Biol., 2, No. 6, 467–475 (2001).

    PubMed  CAS  Google Scholar 

  46. C. Methner, U. Donat, S. B. Felix, and T. Krieg, “Cardioprotection of bradykinin at reperfusion involves transactivation of the epidermal growth factor via matrix metalloproteinase-8,” Acta Physiol. (Oxford), 197, No. 4, 265–271 (2009).

    Article  CAS  Google Scholar 

  47. T. Miki, M. V. Cohen, and J. M. Downey, “Opioid receptors contribute to ischemic preconditioning through protein kinase C activation in rabbits,” Mol. Cell. Biochem., 186, 3–12 (1998).

    Article  PubMed  CAS  Google Scholar 

  48. Y. V. Mukhin, M. Gooz, J. R. Raymond, and M. N. Garnovskaya, “Collagenase-2 and -3 mediate epidermal growth factor receptor transactivation by bradykinin B2 receptor in kidney cells,” J. Pharmacol. Exp. Ther., 318, No. 3, 1033–1043 (2006).

    Article  PubMed  CAS  Google Scholar 

  49. C. E. Murry, R. B. Jennings, and K. A. Reimer, “Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium,” Circulation, 74, No. 5, 1124–1136 (1986).

    Article  PubMed  CAS  Google Scholar 

  50. G. Parenty, S. Appelbe, and G. Milligan, “CXCR2-DOP chemokine receptor antagonism enhances DOP opioid receptor function via allosteric regulation of the CXCR2-DOP receptor heterodimer,” Biochem. J., 412, No. 2, 245–256 (2008).

    Article  PubMed  CAS  Google Scholar 

  51. G. W. Pasternak and Y. X. Pan, “Mix and match: hterodimers and opioid tolerance,” Neuron, 69, No. 1, 6–8 (2011).

    Article  PubMed  CAS  Google Scholar 

  52. J. N. Peart and G. J. Cross, “Adenosine and opioid receptor-mediated cardioprotection in the rat: evidence for cross-talk between receptors,” Am. J. Physiol. Heart Circ. Physiol., 285, No. 1, H81–H89 (2003).

    PubMed  CAS  Google Scholar 

  53. J. N. Peart and G. J. Gross, “Cross-talk between adenosine and opioid receptors,” Drug News Perspect., 18, No. 4, 237–242 (2005).

    Article  PubMed  CAS  Google Scholar 

  54. C. Penna, D. Mancardi, R. Rastaldo, et al., “Intermittent activation of bradykinin B2 receptors and mitochondrial KATP channels trigger cardiac postconditioning through redox signaling,” Cardiovasc. Res., 75, No. 1, 168–177 (2007).

    Article  PubMed  CAS  Google Scholar 

  55. M. Pfeiffer, T. Koch, H. Schröder, et al., “Heterodimerization of somatostatin and opioid receptors cross-modulates phosphorylation, internalization, and desensitization,” J. Biol. Chem., 277, No. 22, 19762–19772 (2002).

    Article  PubMed  CAS  Google Scholar 

  56. S. Philipp, X. M. Yang, L. Cui, et al., “Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2b receptor cascade,” Cardiovasc. Res., 70, No. 2, 308–314 (2006).

    Article  PubMed  CAS  Google Scholar 

  57. N. Prenzel, E. Zwick, H. Daub, et al., “EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF,” Nature, 402, No. 6764, 884–888 (1999).

    PubMed  CAS  Google Scholar 

  58. K. Sato, M. Kimoto, M. Kakumoto, et al., “Adaptor protein Shc undergoes translocation and mediates up-regulation of the tyrosine kinase c-Src in EGF-stimulated A431 cells,” Genes Cells, 5, No. 9, 749–764 (2000).

    Article  PubMed  CAS  Google Scholar 

  59. J. E. Schultz, A. K. Hsu, and G. J. Gross, “Ischemic preconditioning is mediated by a peripheral opioid receptor mechanism in the intact rat heart,” J. Mol. Cell. Cardiol., 29, No. 8, 1355–1362 (1997).

    Article  PubMed  CAS  Google Scholar 

  60. R. Schulz, H. Post, C. Vahlhaus, and G. Heusch, “Ischemic preconditioning in pigs: a graded phenomenon: its relation to adenosine and bradykinin,” Circulation, 98, No. 10, 1022–1029 (1998).

    Article  PubMed  CAS  Google Scholar 

  61. B. Shen, L. M. Harrison-Bernard, A. J. Fuller, et al., “The bradykinin B2 receptor gene is a target of angiotensin II type 1 receptor signaling,” J. Am. Soc. Nephrol., 18, No. 4, 1140–1149 (2007).

    Article  PubMed  CAS  Google Scholar 

  62. Y. M. Tsutsumi, T. Yokoyama, Y. Horikawa, et al., “Reactive oxygen species trigger ischemic and pharmacological postconditioning: in vivo and in vitro characterization,” Life Sci., 81, No. 15, 1223–1227 (2007).

    Article  PubMed  CAS  Google Scholar 

  63. H. L. Wang, C. Y. Hsu, P. C. Huang, et al., “Heterodimerization of opioid receptor-like 1 and μ-opioid receptors impairs the potency of μ-receptor agonist,” J. Neurochem., 92, No. 6, 1285–1294 (2005).

    Article  PubMed  CAS  Google Scholar 

  64. J. Wang, Q. Gao, J. Shen, et al., “Kappa-opioid receptor mediates the cardioprotective effect of ischemic postconditioning,” J. Zhejiang Univer. Med. Sci., 36, No. 1, 41–47 (2007).

    Google Scholar 

  65. S. P. Welch, “Blockade of cannabinoid-induced antinociception by norbinaltorphimine, but not N,N-diallyl-tyrosine-Aib-phenylalanineleucine, ICI 174864 or naloxone in mice,” 265, No. 2, 633–640 (1993).

  66. G. Williams-Pritchard, J. Headrick, and J. N. Peart, “Myocardial opioid receptors in conditioning and cytoprotection,” Pharmaceuticals, 4, No. 3, 470–484 (2011).

    Article  CAS  Google Scholar 

  67. G. Williams-Pritchard, M. Knight, L. S. Hoe, et al., “Essential role of EGFR in cardioprotection and signaling responses to A1 adenosine receptors and ischemic preconditioning,” Am. J. Physiol. Heart Circ. Physiol., 300, No. 6, H2161–H2168 (2011).

    Article  PubMed  CAS  Google Scholar 

  68. K. Q. Xie, L. M. Zhang,Y. Cao, et al., “Adenosine A1 receptor-mediated transactivation of the EGF receptor produces a neuroprotective effect on cortical neurons in vitro,” Acta Pharmacol. Sin., 30, No. 7, 889–898 (2009).

    Article  PubMed  CAS  Google Scholar 

  69. A. J. Zatta, H. Kin, D. Yoshishige, et al., “Evidence that cardioprotection by postconditioning involves preservation of myocardial opioid content and selective opioid receptor activation,” Am. J. Physiol. Heart Circ. Physiol., 294, No. 3, H1444–H1451 (2008).

    Article  PubMed  CAS  Google Scholar 

  70. Z. Q. Zhao, J. C. Corvera, M. E. Halkos, et al., “Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning,” Am. J. Physiol. Heart Circ. Physiol., 285, No. 2, H579–H588 (2003).

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Research Institute of Cardiology, Siberian Branch, Russian Academy of Medical Sciences, 111 Kievskaya Street, 634012, Tomsk, Russia

    L. N. Maslov, A. V. Krylatov, A. Yu. Lishmanov, E. I. Barzakh & N. V. Naryzhnaya

  2. Heart Foundation Research Center, Griffith University, Gold Coast, Australia

    J. P. Headrick

  3. Department of Medicinal Chemistry and Natural Products, Hebrew University of Jerusalem, Ein Kerem, 91120, Jerusalem, Israel

    R. Mechoulam

  4. Department of Physiology, Hebei Medical University, 050017, Shijiazhuang, Hebei Province, China

    Yi Zhang

Authors
  1. L. N. Maslov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. P. Headrick
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Mechoulam
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. V. Krylatov
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Yu. Lishmanov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E. I. Barzakh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. N. V. Naryzhnaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. N. Maslov.

Additional information

Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 98, No. 3, pp. 305–317, March, 2012.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maslov, L.N., Headrick, J.P., Mechoulam, R. et al. The Role of Receptor Transactivation in the Cardioprotective Effects of Preconditioning and Postconditioning. Neurosci Behav Physi 43, 1015–1022 (2013). https://doi.org/10.1007/s11055-013-9844-7

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-013-9844-7

Keywords

Search

Navigation