Skip to main content
Log in

Protective effects of calcitonin gene-related peptide-mediated evodiamine on guinea-pig cardiac anaphylaxis

  • Original Article
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

Previous investigations have indicated that the pharmacological effects of evodiamine, a major alkaloidal component of the dried, unripe fruit of Evodia rutaecarpa Bentham (Rutaceae), are associated with stimulation of calcitonin gene-related peptide (CGRP) release and CGRP prevents cardiac anaphylactic injury. In the present study, the protective effects of evodiamine on cardiac anaphylaxis were examined. Presensitized guinea-pig hearts challenged with specific antigen (bovine serum albumin) caused a marked decrease in coronary flow, left ventricular pressure and its derivatives (±dp/dtmax), an increase in heart rate, and prolongation of P-R interval. Evodiamine (0.3 μM or 1 μM) markedly increased the content of CGRP in the coronary effluent concomitantly with a significant improvement of cardiac function and alleviation of the extension of P-R interval. Evodiamine at the concentration of 1 μM also inhibited the sinus tachycardia. The protective effect of evodiamine on cardiac anaphylaxis was abolished by CGRP8–37, the selective CGRP receptor antagonist. These results suggest that evodiamine possesses a protective effect of cardiac anaphylactic injury and that the effect of evodiamine is related to stimulation of CGRP release.

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

Access this article

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.

Similar content being viewed by others

References

  • Abend Y, Ashkenazy Y, Witzling V, Feigl D, Geltner D, Moshonov S, Zor U (1996) Nitric oxide: a mediator in anaphylactic shock in guinea pigs. J Basic Clin Physiol Pharmacol 7:57–69

    CAS  PubMed  Google Scholar 

  • Capurro N, Levi R (1975) The heart as a target organ in systemic allergic reaction: comparison of cardiac anaphylaxis in vivo and in vitro. Circ Res 36:520–528

    CAS  PubMed  Google Scholar 

  • Chiou WF, Chou CJ, Shum AY, Chen CF (1992) The vasorelaxant effect of evodiamine in rat isolated mesenteric arteries: mode of action. Eur J Pharmacol 215:277–283

    Article  CAS  PubMed  Google Scholar 

  • Chiou WF, Liao JF, Chen CF (1996) Comparative study of the vasodilatory effects of three quinazoline alkaloids isolated from Evodia rutaecarpa. J Nat Prod 59:374–378

    Article  CAS  PubMed  Google Scholar 

  • Cooper DJ (1993) Cardiac dysfunction during anaphylaxis in patients. Appl Cardiopulm Pathophysiol 5:9–18

    Google Scholar 

  • Dai W, Zhou FW, Song QJ, Li YJ, Deng HW, Xiong XM (2000) Protective effects of calcitonin gene-related peptide on guinea-pig cardiac anaphylaxis. Naunyn-Schmiedebergs Arch Pharmacol 361:161–165

    Article  CAS  Google Scholar 

  • Endou M, Poli E, Levi R (1994) Histamine H3 receptor signaling in the heart: possible involvement of Gi/Go proteins and N-type Ca channels. J Pharmacol Exp Ther 269:221–229

    Google Scholar 

  • Felix S, Baumann G, Helmus S, Sattelberger U (1998) The role of histamine in cardiac anaphylaxis: characterization of histaminergic H1 and H2 effects. Basic Res Cardiol 83:531–539

    Google Scholar 

  • Gibson SJ, Polak JM, Bloom SR, Sabate IM, Mulderry PM, Ghateri MA, McGregor GP (1984) Calcitonin gene-related peptide immunoreactivity in the spinal cord of man and eight other species. J Neurosci 4:3101–3111

    CAS  PubMed  Google Scholar 

  • Heller LJ, Regal JF (1988) Effect of adenosine on histamine release and atrioventricular conduction during guinea pig cardiac anaphylaxis. Circ Res 62:1147–1158

    CAS  PubMed  Google Scholar 

  • Hu CP, Xiao L, Deng HW, Li YJ (2002) The cardioprotection of rutaecarpine is mediated by endogenous calcitonin gene-related peptide through activation of vanilloid receptors in guinea-pig hearts. Planta Med 68:705−709

    Article  CAS  PubMed  Google Scholar 

  • Hughes PJ, Holgate ST, Church MK (1984) Adenosine inhibits and potentiates IgE-department histamine release from human lung mast cells by an A2-purinoceptor mediated mechanism. Biochem Pharmacol 33:3847–3852

    Article  CAS  PubMed  Google Scholar 

  • Jeng KF, Lin YH, Lin LC, Chou CJ, Tsai TH, Chen CF (1995) High-performance liquid chromatographic determination of evodiamine in rat plasma: application to pharmacokinetic studies. J Chromatogr B Biomed Appl 668:343–345

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi Y, Nakano Y, Hoshikuma K, Yokoo Y, Kamiya T (2000) The bronchoconstrictive action of evodiamine, an indoloquinazoline alkaloid isolated from the Evodia rutaecarpa, on guinea-pig isolated bronchus: possible involvement of vanilloid receptors. Planta Med 66:526–530

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi Y, Hoshikuma K, Nakano Y, Yokoo Y, Toshikazu Kamiya (2001a) The positive inotropic and chronotropic effects of evodiamine and rutaecarpine, indoloquinazoline alkaloids isolated from the fruits of Evodia rutaecarpa, on the guinea-pig isolated right atria: possible involvement of vanilloid receptors. Planta Med 67:244–248

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi Y, Nakano Y, Kizaki M, Hoshikuma K, Yokoo Y, Kamiya T (2001b) Capsaicin-like anti-obese activities of evodiamine from fruits of Evodia rutaecarpa, a vanilloid receptor agonist. Planta Med 67:628–633

    Article  CAS  PubMed  Google Scholar 

  • Li YJ, Xiao ZS, Peng CF, Deng HW (1996) Calcitonin gene-related-induced preconditioning protects against ischemia-reperfusion injury in isolated rat hearts. Eur J Pharmacol 311:163–167

    CAS  PubMed  Google Scholar 

  • Marone G, de Crescenzo G, Patella V, Arbustini E, Genovese A (1995) Immunological characterization and functional importance of human heart mast cells. Immunopharmacology 31:1–18

    CAS  PubMed  Google Scholar 

  • Matsuda H, Wu JX, Tanaka T, Iinuma M, Kubo M (1997) Antinociceptive activities of 70% methanol extract of evodiae fructus (fruit of Evodia rutaecarpa var. bodinieri) and its alkaloidal components. Biol Pharm Bull 20:243–248

    CAS  PubMed  Google Scholar 

  • McLeod R, Gertner S, Hey J (1993) Production by R-α methylhistamine of a histamine H3 receptor mediated decrease in basal vascular resistance in guinea-pigs. Br J Pharmacol 110:553–558

    CAS  PubMed  Google Scholar 

  • Mest HJ, Picke K, Hoffmmann I, Meissner N, Giessler C (1995) Relevance of mediators to cardiac parameters of isolated anaphylactic guinea-pig heart. Prostaglandins Leukot Essent Fatty Acids 53:21–29

    CAS  PubMed  Google Scholar 

  • Peng CF, Li YJ, Deng HW, Xiong Y (1996) The protective effects of ischemic and calcitonin gene-related peptide preconditioning on myocardial injury by endothelin-1 the isolated perfused rat heart. Life Sci 59:1507–1514

    CAS  PubMed  Google Scholar 

  • Peng CF, Liu GZ, LU R, Li YJ, Deng HW (1998) Protection of calcitonin gene-related peptide-mediated preconditioning against lysophosphatidylcholine-induced myocardial injury in isolated rat hearts. Chin J Pharmacol Toxicol 12:81–84

    CAS  Google Scholar 

  • Ren YS, Ma TG, Wang HB, Yu SQ (1993) Protective effects of calcitonin gene-related peptide (CGRP) on myocardial cell injury and calcium and magnesium contents following severe hypoxia and simulated reperfusion. Med Sci Res 21:177–180

    CAS  Google Scholar 

  • Rubin LE, Levi R (1995) Protective role of bradykinin in cardiac anaphylaxis: coronary-vasodilating and antiarrhythmic activities mediated by autocrine/paracrine mechanisms. Circ Res 76:434–440

    CAS  PubMed  Google Scholar 

  • Schuligoi R, Amann R, Donnerer J, Peskar BA (1997) Release of calcitonin gene-related peptide in cardiac anaphylaxis. Naunyn-Schmiedebergs Arch Pharmacol 355:224–229

    CAS  Google Scholar 

  • Shore PA, Burkhalter A Jr, Cohn VH (1959) A method for the fluorometric assay of histamine in tissues. J Pharmacol Exp Ther 127:182–186

    CAS  Google Scholar 

  • Tao ZW, Li YJ, Deng HW (1997) Attenuation of myocardial injury due to oxygen free radicals (OFR) by pretreatment with OFR or calcitonin gene-related peptide. Acta Pharmacol Sin 18:312–316

    CAS  Google Scholar 

  • Tucker A, Weir E, Reeves J, Grover F (1975) Histamine H1 and H2 receptors in pulmonary and systemic vasculature of the dog. Am J Physiol 229:1008–1013

    CAS  PubMed  Google Scholar 

  • Wharton J, Gulbenkian S, Mulderry PK, Ghatei MA, McGregor GP, Bloom SR, Polak JM (1986) Capsaicin induces a depletion of calcitonin gene-related peptide (CGRP)-immunoreactive nerves in the cardiovascular system of the guinea pig and rat. J Auton Pharmacol Sin 17:289–309

    Google Scholar 

  • Wolff AA, Levi R (1986) Histamine and cardiac arrhythmias. Circ Res 58:1–16

    CAS  PubMed  Google Scholar 

  • Xiao J, Zhou ZH, Ye F, Deng HW, Li YJ (2001) On the mechanism of the protective effects of nitroglycerin and nicorandil in cardiac anaphylaxis. Naunyn-Schmiedebergs Arch Pharmacol 363:407–413

    Article  CAS  Google Scholar 

  • Yaacob HB, Piper PJ (1988) Inhibition of leukotriene release in anaphylactic guinea-pig hearts by a 5-lipoxygenase inhibitor, CGS8515. Br J Pharmacol 95:1322–1328

    CAS  PubMed  Google Scholar 

  • Yallampalli C, Chauhan M, Thota CS, Kondapaka S, Wimalawansa SJ (2002) Calcitonin gene-related peptide in pregnancy and its emerging receptor heterogeneity. Trends Endocrinol Metab 13:263–269

    Article  CAS  PubMed  Google Scholar 

  • Yamahara J, Yamada T, Kitani T, Naitoh Y, Fujimura H (1989) Antianoxic action of evodiamine, an alkaloid in Evodia rutaecarpa fruit. J Ethnopharmacol 27:185–192

    Article  CAS  PubMed  Google Scholar 

  • Yang DL, Tang YH, Li YJ, Deng HW (1996) Protection of calcitonin gene-related peptide induced pretreatment against myocardial injury due to adriamycin in isolated rat hearts. J Chin Pharm Sci 5:150–153

    CAS  Google Scholar 

  • Zaidi M, Seth R, Girgis SI, Self CH (1990) Development and performance of a highly sensitive and specific two-site immunometric assay of calcitonin gene-related peptide. Clin Chem 36:1288−1294

    CAS  PubMed  Google Scholar 

  • Zhang JF, Liu J, Liu XZ, Li MY, Sheng SL, Zhang WJ (1994) The effect of calcitonin gene-related peptide on ischemic reperfusion-induced arrhythmias in rats. Int J Cardiol 46:33–36

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from the Natural Science Foundation No.30200361 and the Ministry of Education, P.R. China.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yuan-Jian Li.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rang, WQ., Du, YH., Hu, CP. et al. Protective effects of calcitonin gene-related peptide-mediated evodiamine on guinea-pig cardiac anaphylaxis. Naunyn-Schmiedeberg's Arch Pharmacol 367, 306–311 (2003). https://doi.org/10.1007/s00210-002-0677-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-002-0677-0

Keywords

Navigation