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01.12.2008 | Experimental

The nociceptin/orphanin FQ-NOP receptor antagonist effects on an animal model of sepsis

verfasst von: Dickson Carvalho, Fabricia Petronilho, Francieli Vuolo, Roberta Albino Machado, Larissa Constantino, Remo Guerrini, Girolamo Calo, Elaine Cristina Gavioli, Emílio Luiz Streck, Felipe Dal-Pizzol

Erschienen in: Intensive Care Medicine | Ausgabe 12/2008

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Abstract

Objective

The aim of this study was investigate the effects of nociceptin/orphanin FQ (N/OFQ) and ([Nphe¹,Arg¹⁴,Lys¹⁵]N/OFQ–NH₂) (UFP-101), the endogenous N/OFQ peptide receptor (NOP) ligand and a selective NOP antagonist, respectively, in the inflammatory response after cecal ligation and puncture (CLP) model of sepsis in rats.

Design

Prospective, controlled experiment.

Setting

Animal basic science laboratory.

Subjects

Male Wistar rats, weighing 300–350 g.

Interventions

Rats subjected to CLP were treated with N/OFQ (0.001, 0.01 or 0.1 mg/kg) or UFP-101 (0.03, 0.03 or 0.3 mg/kg) subcutaneously administered immediately after surgery.

Measurements and main results

Twelve hours after surgery, blood was collected by cardiac puncture and bronchoalveolar (BAL) and peritoneal lavage were performed. In a separate set of experiments mortality was evaluated monitoring CLP rats for 10 days. Our findings showed that UFP-101 (0.03 mg/kg, sc, but not 0.003 mg/kg) modified parameters related to the systemic inflammatory response by effectively preventing cells migration, bacterial dissemination, and by modulating the release of pro-inflammatory cytokines and chemokines, and reducing animal mortality in a clinically relevant model of sepsis. By contrast, N/OFQ (0.1 mg/kg, sc) increased mortality in the CLP model.

Conclusions

Our findings point to a functional relationship between the N/OFQ-NOP receptor system and inflammatory response in the CLP model of sepsis and suggest that NOP receptor antagonists are worthy of testing as innovative drugs for the treatment of sepsis.

Alves-Filho JC, Benjamim C, Tavares-Murta BM, Cunha FQ (2005) Failure of neutrophil migration toward infectious focus in severe sepsis: a critical event for the outcome of this syndrome. Mem Inst Oswaldo Cruz 100:223–226PubMed

Alves-Filho JC, Freitas A, Russo M, Cunha FQ (2006) Toll-like receptor 4 signaling leads to neutrophil migration impairment in polymicrobial sepsis. Crit Care Med 34:461–470PubMedCrossRef

Wagner J, Roth RA (1999) Neutrophil migration during endotoxemia. J Leukoc Biol 66:10–24PubMed

Meunier J, Mollereau C, Toll L, Suaudeau C, Moisand C, Alvinerie P, Butour J, Guillemot J, Ferrara P, Monsarrat B, Mazarguil H, Vassart G, Parmentier M, Costentin J (1995) Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature 377:532–535PubMedCrossRef

Reinscheid RK, Nothacker HP, Bourson A, Ardati A, Henningsen RA, Bunzow JR, Grandy DK, Langen H, Monsma FJ, Civelli O (1995) Orphanin FQ: a neuropeptide that activates an opioidlike G protein-coupled receptor. Science 270:792–794PubMedCrossRef

Giuliani S, Tramontana M, Lecci A, Maggi CA (1997) Effect of nociceptin on heart rate and blood pressure in anaesthetized rats. Eur J Pharmacol 27:177–179CrossRef

Kapusta DR, Sezen SF, Chang JK, Lippton H, Kenigs VA (1997) Diuretic and antinatriuretic responses produced by the endogenous opioid-like peptide, nociceptin (orphanin FQ). Life Sci 60:15–21

Osinski MA, Bass P, Gaumnitz EA (1999) Peripheral and central actions of orphanin FQ (nociceptin) on murine colon. Am J Physiol 276:125–131

Fischer A, Forssmann WG, Undem BJ (1998) Nociceptin-induced inhibition of tachykinergic neurotransmission in guinea pig bronchus. J Pharmacol Exp Ther 285:902–907PubMed

10.

McLeod RL, Parra LE, Mutter JC, Erickson CH, Carey GJ, Tulshian DB, Fawzi AB, Smith-Torhan A, Egan RW, Cuss FM, Hey JA (2001) Nociceptin inhibits cough in the guinea-pig by activation of ORL(1) receptors. Br J Pharmacol 132:1175–1178PubMedCrossRef

11.

Giuliani S, Lecci A, Tramontana M, Maggi CA (1998) The inhibitory effect of nociceptin on the micturition reflex in anaesthetized rats. Br J Pharmacol 124:1566–1572PubMedCrossRef

12.

Peluso J, Gaveriaux-Ruff C, Matthes HW, Filliol D, Kieffer BL (2001) Orphanin FQ/nociceptin binds to functionally coupled ORL1 receptors on human immune cell lines and alters peripheral blood mononuclear cell proliferation. Brain Res Bull 54:655–660PubMedCrossRef

13.

Peluso J, LaForge KS, Matthes HW, Kreek MJ, Kieffer BL, Gaveriaux-Ruff C (1998) Distribuition of nociceptin/orphanin FQ receptor transcript in human central nervous system and immune cells. J Neuroimmunol 81:184–192PubMedCrossRef

14.

Arjomand J, Cole S, Evans CJ (2002) Novel orphanin FQ/nociceptin transcripts are expressed in human immune cells. J Neuroimmunol 130:100–108PubMedCrossRef

15.

Fiset M, Gilbert C, Poubelle PE, Pouliot M (2003) Human neutrophils as a source of nociceptin: a novel link between pain and inflammation. Biochem 42:10498–10505CrossRef

16.

Serhan CN, Fierro IM, Chiang N, Pouliot M (2001) Nociceptin stimulates neutrophil chemotaxis and recruitmant: inhibition by aspirin-triggered-15-epi-lipoxin A ₄ ¹ . J Immunol 166:3650–3654PubMed

17.

Trombella S, Vergura R, Falzarano S, Gerrini R, Calo G, Spisani S (2005) Nociceptin/orphanin FQ stimulates human monocyte chemotaxis via NOP receptor activation. Peptides 26:1497–1502PubMedCrossRef

18.

Waits PS, Purcell WM, Fulford AJ, McLeod JD (2004) Nociceptin/orphanin FQ modulates human T cell function in vitro. J Neuroimmunol 149:110–120PubMedCrossRef

19.

Calo G, Rizzi A, Rizzi D, Bigoni R, Guerrini R, Marzola G, Marti M, McDonald J, Morari M, Lambert DG, Salvadori S, Regoli D (2002) [Nphe1, Arg14, Lys15]nociceptin-NH2, a novel potent and selective antagonist of the nociceptin/orphanin FQ receptor. Br J Pharmacol 136:303–311PubMedCrossRef

20.

Calo G, Gerrini R, Rizzi A, Salvadori S, Burmeister M, Kapusta DR, Lambert DG, Regoli D (2005) UFP-101, a peptide antagonist selective for the nociceptin/orphanin FQ receptor. CNS Drug Rev 11:97–112PubMed

21.

Guerrini R, Calo G, Rizzi A, Bianchi C, Lazarus LH, Salvadori S, Temussi PA, Regoli D (1997) Address and message sequences for the nociceptin receptor: a structure-activity study of nociceptin-(1–13)-peptide amide. J Med Chem 40:1789–1793PubMedCrossRef

22.

Ritter C, Andrades ME, Reinke A, Menna-Barreto S, Moreira JC, Dal-Pizzol F (2004) Treatment with N-acetylcysteine plus deferoxamine protects rats against oxidative stress and improves survival in sepsis. Crit Care Med 32:342–349PubMedCrossRef

23.

Brookes ZL, Stedman EN, Guerrini RG, Lawton BK, Calo G, Lambert DG (2007) Proinflammatory and vasodilator effects of nociceptin/orphanin FQ in the rat mesenteric microcirculation are mediated by histamine. Am J Physiol Heart Circ Physiol 293:2977–2985CrossRef

24.

Godshall CJ, Scott MJ, Peyton JC, Gardner SA, Cheadle WG (2002) Genetic background determines susceptibility during murine septic peritonitis. J Surg Res 102:45–49PubMedCrossRef

25.

Medzhitov R, Janeway C Jr (2000) Innate immune recognition: mechanisms and pathways. Immunol Rev 173:89–97PubMedCrossRef

26.

Goldfarb Y, Reinscheid RK, Kusnecov AW (2006) Orphanin FQ:nociceptin interactions with the immune system in vivo: gene expression changes in lymphoid organs and regulation of the cytokine response to staphylococcal enterotoxin A. J Neuroimmunol 176:76–85PubMedCrossRef

27.

Iseri SO, Sener G, Saglam B, Gedik N, Ercan F, Yeg¡en BC (2005) Oxytocin protects against sepsis-induced multiple organ damage: role of neutrophils. J Surg Res 126:73–81PubMedCrossRef

28.

Aldridge AJ (2002) Role of the neutrophil in septic shock and the adult respiratory distress syndrome. Eur J Surg Res 168:204–214CrossRef

29.

Abraham E (2003) Neutrophils and acute lung injury. Crit Care Med 31:195–199CrossRef

30.

Pampusch MS, Serie JR, Osinski MA, Seybold VS, Murtaugh MP, Brown DR (2000) Expression of nociceptin/OFQ receptor and prepro-nociceptin/OFQ in lymphoid tissues. Peptides 21:1865–1870PubMedCrossRef

31.

Miller TR, Fulford AJ (2007) Regulation of nociceptin/orphaninFQ secretion by immune cells and functional modulation of interleukin-2. Peptides 28:2243–2252PubMedCrossRef

32.

Williams JP, Gold SJ, Young SP, Thompson JP, Lambert DG (2007) Plasma nociceptin concentration in SIRS. Br J Anaest 98:290

33.

Vicent JL (1998) Cardiovascular alterations in septic shock. J Antimicrob Chemother 41(Suppl A):9–15CrossRef

34.

Hashiba E, Hirota K, Kudo T, Calo’ G, Guerrini R, Matsuki A (2003) Effects of nociceptin/orphanin FQ receptor ligands on blood pressure, heart rate, and plasma catecholamine concentrations in guinea pigs. Naunyn Schmiedebergs Arch Pharmacol 367:342–347PubMedCrossRef

35.

Guillou PJ (1993) Biological variation in the development of sepsis after surgery or trauma. Lancet 342:217–220PubMedCrossRef

36.

Schorder J, Kahlke V, Staubach KH, Zabel P, Stuber F (1998) Gender differences in human sepsis. Arch Surg 133:1200–1205CrossRef

37.

Oberholzer A, Keel M, Zellweher R, Steckholzer U, Trentz O, Ertel W (2000) Incidence of septic complications and multiple organ failure in severely injured patients is sex specific. J Trauma 48:932–937PubMedCrossRef

38.

Wichmann MW, Zeilweger R, De Maso CM, Ayala A, Chaudry IH (1996) Enhanced immune responses in females, as opposed to decreased responses in males following hemorrhagic shock and resuscitation. Cytokine 8:853–863PubMedCrossRef

39.

Wichmann MW, Zellweger R, De Maso CM, Chaudry IH (1997) Females in proesterus state maintain splenic immune functions and tolerate sepsis better than males. Crit Care Med 25:106–110PubMedCrossRef

Titel: The nociceptin/orphanin FQ-NOP receptor antagonist effects on an animal model of sepsis
verfasst von: Dickson Carvalho
Fabricia Petronilho
Francieli Vuolo
Roberta Albino Machado
Larissa Constantino
Remo Guerrini
Girolamo Calo
Elaine Cristina Gavioli
Emílio Luiz Streck
Felipe Dal-Pizzol
Publikationsdatum: 01.12.2008
Verlag: Springer-Verlag
Erschienen in: Intensive Care Medicine / Ausgabe 12/2008
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-008-1313-3

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The nociceptin/orphanin FQ-NOP receptor antagonist effects on an animal model of sepsis

Abstract

Objective

Design

Setting

Subjects

Interventions

Measurements and main results

Conclusions

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Springer Medizin

Abstract

Objective

Design

Setting

Subjects

Interventions

Measurements and main results

Conclusions

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