Selective melanocortin MC 4 receptor agonists reverse haemorrhagic shock and prevent multiple organ damage

D. Giuliani, C. Mioni, C. Bazzani, D. Zaffe, A. R. Botticelli, S. Capolongo, A. Sabba, M. Galantucci, A. Iannone, P. Grieco, E. Novellino, G. Colombo, A. Tomasi, A. Catania, S. Guarini

Research output: Contribution to journalArticle

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Abstract

Background and purpose: In circulatory shock, melanocortins have life-saving effects likely to be mediated by MC 4 receptors. To gain direct insight into the role of melanocortin MC 4 receptors in haemorrhagic shock, we investigated the effects of two novel selective MC 4 receptor agonists. Experimental approach: Severe haemorrhagic shock was produced in rats under general anaesthesia. Rats were then treated with either the non-selective agonist [Nle 4, D-Phe 7]α- melanocyte-stimulating hormone (NDP-α-MSH) or with the selective MC 4 agonists RO27-3225 and PG-931. Cardiovascular and respiratory functions were continuously monitored for 2 h; survival rate was recorded up to 24 h. Free radicals in blood were measured using electron spin resonance spectrometry; tissue damage was evaluated histologically 25 min or 24 h after treatment. Key results: All shocked rats treated with saline died within 30-35 min. Treatment with NDP-α-MSH, RO27-3225 and PG-931 produced a dose-dependent (13-108 nmol kg -1 i.v.) restoration of cardiovascular and respiratory functions, and improved survival. The three melanocortin agonists also markedly reduced circulating free radicals relative to saline-treated shocked rats. All these effects were prevented by i.p. pretreatment with the selective MC 4 receptor antagonist HS024. Moreover, treatment with RO27-3225 prevented morphological and immunocytochemical changes in heart, lung, liver, and kidney, at both early (25 min) and late (24 h) intervals. Conclusions and Implications: Stimulation of MC 4 receptors reversed haemorrhagic shock, reduced multiple organ damage and improved survival. Our findings suggest that selective MC 4 receptor agonists could have a protective role against multiple organ failure following circulatory shock.

Original languageEnglish
Pages (from-to)595-603
Number of pages9
JournalBritish Journal of Pharmacology
Volume150
Issue number5
DOIs
Publication statusPublished - Mar 2007

Fingerprint

Receptor, Melanocortin, Type 4
Hemorrhagic Shock
Melanocortins
Melanocyte-Stimulating Hormones
Free Radicals
Shock
Multiple Organ Failure
Electron Spin Resonance Spectroscopy
General Anesthesia
Spectrum Analysis
Kidney
Lung
Liver
butir-His-Phe-Arg-Trp-Sar-NH2
Ac-Nle-c(Asp-Pro-D-Phe-Arg-Trp-Lys)-Pro-Val-NH2

Keywords

  • Free radicals
  • Haemorrhagic shock
  • Melanocortin MC receptors
  • Melanocortin peptides
  • Organ damage

ASJC Scopus subject areas

  • Pharmacology

Cite this

Giuliani, D., Mioni, C., Bazzani, C., Zaffe, D., Botticelli, A. R., Capolongo, S., ... Guarini, S. (2007). Selective melanocortin MC 4 receptor agonists reverse haemorrhagic shock and prevent multiple organ damage. British Journal of Pharmacology, 150(5), 595-603. https://doi.org/10.1038/sj.bjp.0707115

Selective melanocortin MC 4 receptor agonists reverse haemorrhagic shock and prevent multiple organ damage. / Giuliani, D.; Mioni, C.; Bazzani, C.; Zaffe, D.; Botticelli, A. R.; Capolongo, S.; Sabba, A.; Galantucci, M.; Iannone, A.; Grieco, P.; Novellino, E.; Colombo, G.; Tomasi, A.; Catania, A.; Guarini, S.

In: British Journal of Pharmacology, Vol. 150, No. 5, 03.2007, p. 595-603.

Research output: Contribution to journalArticle

Giuliani, D, Mioni, C, Bazzani, C, Zaffe, D, Botticelli, AR, Capolongo, S, Sabba, A, Galantucci, M, Iannone, A, Grieco, P, Novellino, E, Colombo, G, Tomasi, A, Catania, A & Guarini, S 2007, 'Selective melanocortin MC 4 receptor agonists reverse haemorrhagic shock and prevent multiple organ damage', British Journal of Pharmacology, vol. 150, no. 5, pp. 595-603. https://doi.org/10.1038/sj.bjp.0707115
Giuliani, D. ; Mioni, C. ; Bazzani, C. ; Zaffe, D. ; Botticelli, A. R. ; Capolongo, S. ; Sabba, A. ; Galantucci, M. ; Iannone, A. ; Grieco, P. ; Novellino, E. ; Colombo, G. ; Tomasi, A. ; Catania, A. ; Guarini, S. / Selective melanocortin MC 4 receptor agonists reverse haemorrhagic shock and prevent multiple organ damage. In: British Journal of Pharmacology. 2007 ; Vol. 150, No. 5. pp. 595-603.
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AU - Mioni, C.

AU - Bazzani, C.

AU - Zaffe, D.

AU - Botticelli, A. R.

AU - Capolongo, S.

AU - Sabba, A.

AU - Galantucci, M.

AU - Iannone, A.

AU - Grieco, P.

AU - Novellino, E.

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KW - Melanocortin peptides

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