Skip to main content
SpringerLink
Log in

Monophosphoryl Lipid A-Induced Delayed Preconditioning in Rat Small Intestine Is Mediated by Calcitonin Gene-Related Peptide

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Protective effects of ischemic preconditioning in rat small intestine have been shown to be related to the release of calcitonin gene-related peptide.

Aims

The purpose of the present study was to explore whether monophosphoryl lipid A participated in the protective process of the delayed ischemic preconditioning in the peripheral vascular bed (the anse intestinalis of rat), and whether endogenous calcitonin gene-related peptide is a mediator in this process.

Methods

Intestinal ischemia was induced by occlusion of the superior mesenteric artery for 30 min, followed by reperfusion for 60 min. The intestinal lesions were evaluated by the measurement of serum lactate dehydrogenase, myeloperoxidase levels, and small intestine tissue contents of malondialdehyde. In addition, calcitonin gene-related peptide in plasma and superior mesenteric vein effluent were also examined.

Results

Pretreatment with monophosphoryl lipid A (500 μg/kg. i.p.) 24 h prior to ischemia–reperfusion significantly alleviated the intestinal tissue histology lesions, decreased serum levels of lactate dehydrogenase, myeloperoxidase, and reduced tissue content of malondialdehyde. Moreover, monophosphoryl lipid A markedly increased plasma concentrations of calcitonin gene-related peptide. Pretreatment with capsaicin, which specifically depletes the neurotransmitter content of sensory nerves or calcitonin gene-related peptide-(8–37), a selective calcitonin gene-related peptide receptor antagonist, inhibited the increased calcitonin gene-related peptide release and subsequently abrogated the protection by monophosphoryl lipid A.

Conclusions

In conclusion, monophosphoryl lipid A pharmacologically mimics delayed preconditioning and the protective effects are related to the stimulation of calcitonin gene-related peptide release in rat small intestine.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Ishida T, Yarimizu K, Gute DC, Korthuis RJ. Mechanisms of ischemic preconditioning. Shock. 1997;8:86–94.

    Article  PubMed  CAS  Google Scholar 

  2. Koti RS, Seifalian AM, McBride AG, Yang W, Davidson BR. The relationship of hepatic tissue oxygenation with nitric oxide metabolism in ischemic preconditioning of the liver. FASEB J. 2002;16:1654–1656.

    PubMed  CAS  Google Scholar 

  3. Zhao H. The protective effect of ischemic postconditioning against ischemic injury: from the heart to the brain. J Neuroimmune Pharmacol. 2007;2:313–318.

    Article  PubMed  Google Scholar 

  4. Davis JM, Gute DC, Jones S, Krsmanovic A, Korthuis RJ. Ischemic preconditioning prevents postischemic P-selectin expression in the rat small intestine. Am J Physiol. 1999;277:H2476–H2481.

    PubMed  CAS  Google Scholar 

  5. Bolli R. The late phase of preconditioning. Circ Res. 2000;87:972–983.

    PubMed  CAS  Google Scholar 

  6. Luo D, Deng PY, Ye F, Peng WJ, Deng HW, Li YJ. Delayed preconditioning by cardiac ischemia involves endogenous calcitonin gene-related peptide via the nitric oxide pathway. Eur J Pharmacol. 2004;502:135–141.

    Article  PubMed  CAS  Google Scholar 

  7. Dun Y, Hao YB, Wu YX, Zhang Y, Zhao RR. Protective effects of nitroglycerin-induced preconditioning mediated by calcitonin gene-related peptide in rat small intestine. Eur J Pharmacol. 2001;430:317–324.

    Article  PubMed  CAS  Google Scholar 

  8. Zhang Y, Wu YX, Hao YB, Dun Y, Yang SP. Role of endogenous opioid peptides in protection of ischemic preconditioning in rat small intestine. Life Sci. 2001;68:1013–1019.

    Article  PubMed  CAS  Google Scholar 

  9. Yang SP, Hao YB, Wu YX, Dun W, Shen LH, Zhang Y. Ischemic preconditioning mediated by activation of KATP channels in rat small intestine. Zhongguo Yao Li Xue Bao. 1999;20:341–344.

    PubMed  CAS  Google Scholar 

  10. Li J, Zhang M, Yang C, Dun Y, Zhang Y, Hao Y. Nitroglycerin protects small intestine from ischemia-reperfusion injury via NO-cGMP pathway and upregulation of alpha-CGRP. J Gastrointest Surg. 2009;13:478–485.

    Article  PubMed  Google Scholar 

  11. Vlasov TD, Smirnov DA, Nutfullina GM. Preconditioning of the small intestine to ischemia in rats. Neurosci Behav Physiol. 2002;32:449–453.

    Article  PubMed  CAS  Google Scholar 

  12. Li YJ, Peng J. The cardioprotection of calcitonin gene-related peptide-mediated preconditioning. Eur J Pharmacol. 2002;442:173–177.

    Article  PubMed  CAS  Google Scholar 

  13. Madeddu P, Emanueli C, Bonaria SM, et al. Role of calcitonin gene-related peptide and kinins in post-ischemic intestinal reperfusion. Peptides. 2001;22:915–922.

    Article  PubMed  CAS  Google Scholar 

  14. Sharony R, Frolkis I, Froylich D, et al. Pharmacological preconditioning with monophosphoryl lipid A improves post ischemic diastolic function and modifies TNF-alpha synthesis. Eur J Cardiothorac Surg. 2005;27:501–507.

    Article  PubMed  Google Scholar 

  15. Peng J, Lu R, Deng HW, Li YJ. Involvement of alpha-calcitonin gene-related peptide in monophosphoryl lipid A-induced delayed preconditioning in rat hearts. Eur J Pharmacol. 2002;436:89–96.

    Article  PubMed  CAS  Google Scholar 

  16. He SY, Deng HW, Li YJ. Monophosphoryl lipid A-induced delayed preconditioning is mediated by calcitonin gene-related peptide. Eur J Pharmacol. 2001;420:143–149.

    Article  PubMed  CAS  Google Scholar 

  17. Yeo CJ, Couse NF, Zinner MJ. Serotonin and substance P stimulate intestinal secretion in the isolated perfused ileum. Surgery. 1989;105:86–92.

    PubMed  CAS  Google Scholar 

  18. Chiu CJ, McArdle AH, Brown R, Scott HJ, Gurd FN. Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg. 1970;101:478–483.

    PubMed  CAS  Google Scholar 

  19. Mei DA, Elliott GT, Gross GJ. KATP channels mediate late preconditioning against infarction produced by monophosphoryl lipid A. Am J Physiol. 1996;271:H2723–H2729.

    PubMed  CAS  Google Scholar 

  20. Elliott GT, Comerford ML, Smith JR, Zhao L. Myocardial ischemia/reperfusion protection using monophosphoryl lipid A is abrogated by the ATP-sensitive potassium channel blocker, glibenclamide. Cardiovasc Res. 1996;32:1071–1080.

    Article  PubMed  CAS  Google Scholar 

  21. Tosaki A, Maulik N, Elliott GT, Blasig IE, Engelman RM, Das DK. Preconditioning of rat heart with monophosphoryl lipid A: a role for nitric oxide. J Pharmacol Exp Ther. 1998;285:1274–1279.

    PubMed  CAS  Google Scholar 

  22. Maulik N, Tosaki A, Elliott GT, Maulik G, Das DK. Induction of iNOS gene expression by monophosphoryl lipid A: a pharmacological approach for myocardial adaptation to ischemia. Drugs Exp Clin Res. 1998;24:117–124.

    PubMed  CAS  Google Scholar 

  23. Xi L, Jarrett NC, Hess ML, Kukreja RC. Essential role of inducible nitric oxide synthase in monophosphoryl lipid A-induced late cardioprotection: evidence from pharmacological inhibition and gene knockout mice. Circulation. 1999;99:2157–2163.

    PubMed  CAS  Google Scholar 

  24. Li YJ, Song QJ, Xiao J. Calcitonin gene-related peptide: an endogenous mediator of preconditioning. Acta Pharmacol Sin. 2000;21:865–869.

    PubMed  Google Scholar 

  25. Zhou FW, Li YJ, Deng HW. Mediation of calcitonin gene-related peptide in protection of ischemic preconditioning in rat hindlimbs. Zhongguo Yao Li Xue Bao. 1998;19:477–480.

    PubMed  CAS  Google Scholar 

  26. Wang X, Wu Z, Tang Y, Fiscus RR, Han C. Rapid nitric oxide- and prostaglandin-dependent release of calcitonin gene-related peptide (CGRP) triggered by endotoxin in rat mesenteric arterial bed. Br J Pharmacol. 1996;118:2164–2170.

    PubMed  CAS  Google Scholar 

  27. Fanciullacci M, Alessandri M, Figini M, Geppetti P, Michelacci S. Increase in plasma calcitonin gene-related peptide from the extracerebral circulation during nitroglycerin-induced cluster headache attack. Pain. 1995;60:119–123.

    Article  PubMed  CAS  Google Scholar 

  28. Wei EP, Moskowitz MA, Boccalini P, Kontos HA. Calcitonin gene-related peptide mediates nitroglycerin and sodium nitroprusside-induced vasodilation in feline cerebral arterioles. Circ Res. 1992;70:1313–1319.

    PubMed  CAS  Google Scholar 

  29. Booth BP, Tabrizi-Fard MA, Fung H. Calcitonin gene-related peptide-dependent vascular relaxation of rat aorta. An additional mechanism for nitroglycerin. Biochem Pharmaco. 2000;59:1603–1609.

    Article  CAS  Google Scholar 

  30. Doi Y, Peng H, Kudo H, Hamasaki K, Fujimoto S. Expression of alpha-calcitonin gene-related peptide in the enteric nervous system of rat small intestine. Neurosci Lett. 2000;285:33–36.

    Article  PubMed  CAS  Google Scholar 

  31. Elliott GT. Monophosphoryl lipid A induces delayed preconditioning against cardiac ischemia-reperfusion injury. J Mol Cell Cardiol. 1998;30:3–17.

    Article  PubMed  CAS  Google Scholar 

  32. Zimmerman BJ, Anderson DC, Granger DN. Neuropeptides promote neutrophil adherence to endothelial cell monolayers. Am J Physiol. 1992;263:G678–G682.

    PubMed  CAS  Google Scholar 

  33. Sung CP, Arleth AJ, Aiyar N, Bhatnagar PK, Lysko PG, Feuerstein G. CGRP stimulates the adhesion of leukocytes to vascular endothelial cells. Peptides. 1992;13:429–434.

    Article  PubMed  CAS  Google Scholar 

  34. Kamada K, Gaskin FS, Yamaguchi T, et al. Role of calcitonin gene-related peptide in the postischemic anti-inflammatory effects of antecedent ethanol ingestion. Am J Physiol Heart Circ Physiol. 2006;290:H531–H537.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Shanxi Medical University, 030001, Taiyuan, Shanxi, China

    Cai-Hong Yang, Ming-Sheng Zhang, Jie Li, Xuan-Ping Zhang & Yi-Bin Hao

  2. National Human Genomics Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Hang Wang

Authors
  1. Cai-Hong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ming-Sheng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jie Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xuan-Ping Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yi-Bin Hao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yi-Bin Hao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yang, CH., Zhang, MS., Li, J. et al. Monophosphoryl Lipid A-Induced Delayed Preconditioning in Rat Small Intestine Is Mediated by Calcitonin Gene-Related Peptide. Dig Dis Sci 56, 1333–1341 (2011). https://doi.org/10.1007/s10620-010-1428-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-010-1428-6

Keywords

Search

Navigation