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Canadian journal of veterinary research = Revue canadienne de recherche veterinaire2009; 73(1); 25-33;

Neurokinin receptors in recurrent airway obstruction: a comparative study of affected and unaffected horses.

Abstract: The purpose of the study was to compare in vitro airway responses to neurokinin A & B (NKA and NKB) and expression of NK-2 receptors in airways of horses affected and unaffected with recurrent airway obstruction (RAO). Neurokinin-A, an inflammatory mediator belonging to the tachykinin family of neuropeptides, causes bronchoconstriction by binding to NK-2 receptors. Neurokinin-B is a lesser-known neuropeptide that acts on NK-3 receptors. Horses were placed into RAO-affected and RAO-unaffected groups based on their history, clinical scoring, and pulmonary function testing. Lung tissue from each lobe was collected for immunohistochemical staining for NK-2 receptors. Cumulative concentration-response relationships were determined on bronchial rings (4-mm wide) collected and prepared from the right diaphragmatic lung lobe to graded concentrations (half log molar concentrations 10(-7)M to 10(-4)M) of NKA and NKB. The results showed that NKA caused significantly greater contraction than NKB in both groups. In RAO-affected horses, both agents produced significantly greater bronchial contractions than those in the RAO-unaffected horses. Immunohistochemical staining showed that the overall NK-2 receptor distribution was significantly increased in bronchial epithelium and smooth muscles of bronchi and pulmonary vessels of RAO-affected than RAO-unaffected horses. The findings indicate that NK-2 receptors are up-regulated in RAO, suggesting that NK-2 receptor antagonists may have some therapeutic value in controlling the progression of airway hyperreactivity in horses affected with RAO. Le but de la présente étude était de comparer les réponses aux neurokinines A & B (NKA et NKB) et l’expression des récepteurs NK-2 dans les voies respiratoires de chevaux affectés et non-affectés d’obstructions récurrentes des voies respiratoires (RAO). NKA est un médiateur neuropeptidique de l’inflammation appartenant à la famille des tachykinines causant une broncho-constriction en se liant aux récepteurs de NK-2. Le regroupement des chevaux selon qu’ils soient affectés ou non de RAO a été effectué sur la base de leur histoire, l’évaluation clinique et des tests de fonctions pulmonaires. Des échantillons de tissu pulmonaire provenant de chaque lobe ont été prélevés pour coloration immuno-histochimique pour les récepteurs de NK-2. Les relations cumulatives concentration-réponse ont été déterminées sur des anneaux bronchiques (4 mm de largeur) prélevés et préparés à partir du lobe pulmonaire diaphragmatique droit à des concentrations graduées (concentrations molaires semi-logarithmiques de 10M à 10M) de NKA et NKB, un neuropeptide moins connu agissant sur les récepteurs NK-3. Les résultats ont montré que NKA cause une contraction significativement plus grande que NKB dans les deux groupes. Chez les chevaux atteints de RAO, les deux agents ont produit une contraction plus importante que les animaux témoins. Une coloration immuno-histochimique a montré que la distribution globale des récepteurs à NK-2 était significativement plus grande dans l’épithélium bronchique et les muscles lisses des bronches et des vaisseaux pulmonaires des chevaux affectés par RAO que de ceux qui n’en sont pas affectés. Ces résultats indiquent que les récepteurs pour NK-2 sont régulés à la hausse lors de RAO, ce qui suggère que des antagonistes pour les récepteurs à NK-2 pourraient avoir une certaine valeur thérapeutique en contrôlant la progression de l’hyperactivité des voies respiratoires chez les chevaux atteints de RAO. (Traduit par Docteur Serge Messier)
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Publication Date: 2009-04-02 PubMed ID: 19337392PubMed Central: PMC2613593
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study explores the difference in airway responses to neurokinin A & B and the expression of NK-2 receptors in horses affected by recurrent airway obstruction (RAO) against those not affected by it, suggesting that NK-2 receptor antagonists could potentially manage the progression of airway overreactivity in RAO-affected horses.

Overview of the Research Procedure

  • The horses were grouped into RAO-affected and RAO-unaffected groups based on their past records, clinical scoring, and lung function tests.
  • Lung tissue from each lobe was collected for immunohistochemical staining for NK-2 receptors. This is a technique used to visualize proteins in cells of a tissue, which in this case were the NK-2 receptors involved in bronchoconstriction.
  • The researchers then determined the cumulative concentration-response relationships on bronchial rings collected and prepared from the right diaphragmatic lung lobe. These were exposed to different graded concentrations of NKA and NKB, neuropeptides involved in inflammation and bronchoconstriction.

Findings of the Study

  • The results showed that neurokinin A (NKA) induced significantly greater contraction than neurokinin B (NKB) in horses from both the RAO-affected and RAO-unaffected groups.
  • In RAO-affected horses, both NKA and NKB resulted in significantly greater bronchial contractions than in RAO-unaffected horses.
  • Immunohistochemical staining revealed a significantly higher distribution of NK-2 receptors in the bronchial epithelium and smooth muscles of bronchi and lung vessels in RAO-affected horses than in the unaffected ones.

Implications of the Study

  • The findings suggest that NK-2 receptors, which NKA binds to cause bronchoconstriction, are up-regulated in horses affected by RAO.
  • Therefore, the study implies that antagonists for NK-2 receptors – substances that block the receptors’ activity – might have a therapeutic value in controlling the progression of increased airway sensitivity in horses suffering from RAO.

Cite This Article

APA
Venugopal CS, Holmes EP, Polikepahad S, Laborde S, Kearney M, Moore RM. (2009). Neurokinin receptors in recurrent airway obstruction: a comparative study of affected and unaffected horses. Can J Vet Res, 73(1), 25-33.

Publication

Canadian journal of veterinary research = Revue canadienne de recherche veterinaire
ISSN: 1928-9022
NlmUniqueID: 8607793
Country: Canada
Language: English
Volume: 73
Issue: 1
Pages: 25-33

Researcher Affiliations

Venugopal, Changaram S
  • Equine Health Studies Program, Departments of Veterinary Clinical Science and Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803, USA. cvenugopal@vetmed.lsu.edu
Holmes, Earnestine P
    Polikepahad, Sumanth
      Laborde, Susan
        Kearney, Michael
          Moore, Rustin M

            MeSH Terms

            • Airway Obstruction / pathology
            • Airway Obstruction / physiopathology
            • Airway Obstruction / veterinary
            • Animals
            • Antibodies / blood
            • Bronchi / drug effects
            • Bronchi / physiopathology
            • Bronchial Hyperreactivity / pathology
            • Bronchial Hyperreactivity / physiopathology
            • Bronchial Hyperreactivity / veterinary
            • Horse Diseases / pathology
            • Horse Diseases / physiopathology
            • Horses
            • Immunohistochemistry
            • Muscle, Smooth / drug effects
            • Muscle, Smooth / physiopathology
            • Neurokinin A / pharmacology
            • Neurokinin B / pharmacology
            • Nose / physiopathology
            • Receptors, Neurokinin-2 / physiology
            • Recurrence
            • Respiratory Physiological Phenomena

            References

            This article includes 35 references
            1. Buechner-Maxwell V. Airway hyperresponsiveness. Compend Contin Educ Pract Vet 1993;15:1379–1389.
            2. Robinson NE. Recurrent airway obstruction (heaves). In: Lekeux P, editor. Equine Respiratory Diseases. Ithaca, New York: International Veterinary Information Service; 2001. ( www.ivis.org) doc B0317.1101.
            3. Kaup FJ, Drommer W, Deegen E. Ultrastructural findings in horses with chronic obstructive pulmonary disease (COPD). I: Alterations of the larger conducting airways.. Equine Vet J 1990 Sep;22(5):343-8.
              pubmed: 2226399doi: 10.1111/j.2042-3306.1990.tb04287.xgoogle scholar: lookup
            4. Naylor JM, Clark EG, Clayton HM. Chronic obstructive pulmonary disease: Usefulness of clinical signs, bronchoalveolar lavage, and lung biopsy as diagnostic and prognostic aids.. Can Vet J 1992 Sep;33(9):591-8.
              pmc: PMC1481327pubmed: 17424075
            5. Beadle RE. Summer pasture-associated obstructive pulmonary disease. In: Robinson NE, editor. Current Therapy in Equine Medicine. Philadelphia, Pennsylvania: WB Saunders; 1983. pp. 512–516.
            6. Seahorn TL, Beadle RE. Summer pasture-associated obstructive pulmonary disease. Equine Pract 1994;16:39–41.
            7. Costa LR, Seahorn TL, Moore RM, Taylor HW, Gaunt SD, Beadle RE. Correlation of clinical score, intrapleural pressure, cytologic findings of bronchoalveolar fluid, and histopathologic lesions of pulmonary tissue in horses with summer pasture-associated obstructive pulmonary disease.. Am J Vet Res 2000 Feb;61(2):167-73.
              pubmed: 10685689doi: 10.2460/ajvr.2000.61.167google scholar: lookup
            8. Venugopal CS, Polikepahad S, Holmes EP, Heuvel JV, Leas TL, Moore RM. Endothelin receptor alterations in equine airway hyperreactivity.. Can J Vet Res 2006 Jan;70(1):50-7.
              pmc: PMC1325094pubmed: 16548332
            9. Kraneveld AD, Nijkamp FP, Van Oosterhout AJ. Role for neurokinin-2 receptor in interleukin-5-induced airway hyperresponsiveness but not eosinophilia in guinea pigs.. Am J Respir Crit Care Med 1997 Aug;156(2 Pt 1):367-74.
              pubmed: 9279211doi: 10.1164/ajrccm.156.2.9608101google scholar: lookup
            10. Maggi CA, Giachetti A, Dey RD, Said SI. Neuropeptides as regulators of airway function: vasoactive intestinal peptide and the tachykinins.. Physiol Rev 1995 Apr;75(2):277-322.
              pubmed: 7724664doi: 10.1152/physrev.1995.75.2.277google scholar: lookup
            11. Advenier C, Lagente V, Boichot E. The role of tachykinin receptor antagonists in the prevention of bronchial hyperresponsiveness, airway inflammation and cough.. Eur Respir J 1997 Aug;10(8):1892-906.
              pubmed: 9272936doi: 10.1183/09031936.97.10081892google scholar: lookup
            12. Krishnakumar S, Holmes EP, Moore RM, Kappel L, Venugopal CS. Non-adrenergic non-cholinergic excitatory innervation in the airways: role of neurokinin-2 receptors.. Auton Autacoid Pharmacol 2002 Aug;22(4):215-24.
              pubmed: 12656947doi: 10.1046/j.1474-8673.2002.00262.xgoogle scholar: lookup
            13. Maggi CA, Patacchini R, Rovero P, Santicioli P. Tachykinin receptors and noncholinergic bronchoconstriction in the guinea-pig isolated bronchi.. Am Rev Respir Dis 1991 Aug;144(2):363-7.
              pubmed: 1713430doi: 10.1164/ajrccm/144.2.363google scholar: lookup
            14. Zhang Y, Berger A, Milne CD, Paige CJ. Tachykinins in the immune system.. Curr Drug Targets 2006 Aug;7(8):1011-20.
              pubmed: 16918329doi: 10.2174/138945006778019363google scholar: lookup
            15. Nakanishi S. Mammalian tachykinin receptors.. Annu Rev Neurosci 1991;14:123-36.
              pubmed: 1851606doi: 10.1146/annurev.ne.14.030191.001011google scholar: lookup
            16. Venugopal CS, Moore RM, Holmes EP, Koch CE, Seahorn TL, Beadle RE. Comparative responses of bronchial rings to mediators of airway hyperreactivity in healthy horses and those affected with summer pasture-associated obstructive pulmonary disease.. Am J Vet Res 2001 Feb;62(2):259-63.
              pubmed: 11212036doi: 10.2460/ajvr.2001.62.259google scholar: lookup
            17. Zhu FX, Zhang XY, Olszewski MA, Robinson NE. Mechanism of capsaicin-induced relaxation in equine tracheal smooth muscle.. Am J Physiol 1997 Nov;273(5):L997-1001.
              pubmed: 9374726doi: 10.1152/ajplung.1997.273.5.l997google scholar: lookup
            18. Seahorn TL, Beadle RE, McGorum BC, Marley CL. Quantification of antigen-specific antibody concentrations in tracheal lavage fluid of horses with summer pasture-associated obstructive pulmonary disease.. Am J Vet Res 1997 Dec;58(12):1408-11.
              pubmed: 9401689
            19. Portbury AL, Furness JB, Southwell BR, Wong H, Walsh JH, Bunnett NW. Distribution of neurokinin-2 receptors in the guinea-pig gastrointestinal tract.. Cell Tissue Res 1996 Dec;286(3):281-92.
              pubmed: 8929331doi: 10.1007/s004410050698google scholar: lookup
            20. Ollerenshaw SL, Jarvis D, Sullivan CE, Woolcock AJ. Substance P immunoreactive nerves in airways from asthmatics and nonasthmatics.. Eur Respir J 1991 Jun;4(6):673-82.
              pubmed: 1716217
            21. Polikepahad S, Paulsen DB, Moore RM, Costa LR, Venugopal CS. Immunohistochemical determination of the expression of endothelin receptors in bronchial smooth muscle and epithelium of healthy horses and horses affected by summer pasture-associated obstructive pulmonary disease.. Am J Vet Res 2006 Feb;67(2):348-57.
              pubmed: 16454644doi: 10.2460/ajvr.67.2.348google scholar: lookup
            22. Uddman R, Hakanson R, Luts A, Sundler F. Distribution of neuropeptides in airways. In: Barnes PJ, editor. Autonomic Control of the Respiratory System. London: Informa Health Care; 1997. pp. 21–37.
            23. Maggi CA, Meli A. The sensory-efferent function of capsaicin-sensitive sensory neurons.. Gen Pharmacol 1988;19(1):1-43.
              pubmed: 3278943doi: 10.1016/0306-3623(88)90002-xgoogle scholar: lookup
            24. Szolcsanyi J. Capsaicin-sensitive chemoceptive neural system with dual sensory-efferent function. In: Chahl LA, Szolcsanyi J, Lembeck F, editors. Antidromic Vasodilatation and Neurogenic Inflammation. Budapest: Akademiai Kiado; 1984. pp. 26–52.
            25. Verones B, Oortgiesen M. Neurogenic inflammation and particulate matter (PM) air pollutants.. Neurotoxicology 2001 Dec;22(6):795-810.
              pubmed: 11829413doi: 10.1016/s0161-813x(01)00062-6google scholar: lookup
            26. Moussaoui S, Carruette A, Garret C. Further evidence that substance P is a mediator of both neurogenic inflammation and pain: two phenomena inhibited either by postsynaptic blockade of NK1 receptors or by presynaptic action of opioid receptor agonists.. Regul Pept 1993 Jul 2;46(1-2):424-5.
              pubmed: 7692556doi: 10.1016/0167-0115(93)90108-kgoogle scholar: lookup
            27. Solway J, Leff AR. Sensory neuropeptides and airway function.. J Appl Physiol (1985) 1991 Dec;71(6):2077-87.
              pubmed: 1663932doi: 10.1152/jappl.1991.71.6.2077google scholar: lookup
            28. Bai TR, Zhou D, Weir T, Walker B, Hegele R, Hayashi S, McKay K, Bondy GP, Fong T. Substance P (NK1)- and neurokinin A (NK2)-receptor gene expression in inflammatory airway diseases.. Am J Physiol 1995 Sep;269(3 Pt 1):L309-17.
              pubmed: 7573463doi: 10.1152/ajplung.1995.269.3.l309google scholar: lookup
            29. Watson N, Maclagan J, Barnes PJ. Endogenous tachykinins facilitate transmission through parasympathetic ganglia in guinea-pig trachea.. Br J Pharmacol 1993 Jul;109(3):751-9.
              pmc: PMC2175621pubmed: 7689402doi: 10.1111/j.1476-5381.1993.tb13638.xgoogle scholar: lookup
            30. Barnes PJ, Belvisi MG, Rogers DF. Modulation of neurogenic inflammation: novel approaches to inflammatory disease.. Trends Pharmacol Sci 1990 May;11(5):185-9.
              pubmed: 2248639doi: 10.1016/0165-6147(90)90112-lgoogle scholar: lookup
            31. Barnes PJ. Neurogenic inflammation and asthma.. J Asthma 1992;29(3):165-80.
              pubmed: 1351052doi: 10.3109/02770909209099025google scholar: lookup
            32. Meggs WJ. Neurogenic inflammation and sensitivity to environmental chemicals.. Environ Health Perspect 1993 Aug;101(3):234-8.
              pmc: PMC1519776pubmed: 8404760doi: 10.1289/ehp.93101234google scholar: lookup
            33. Barnes PJ. NANC nerves and neuropeptides. In: Barnes PJ, Rogers IW, Thompson NC, editors. Asthma: Basic mechanisms and clinical management. London: Acad Pr; 1998. 1998. pp. 423–458.
            34. Di Maria GU, Bellofiore S, Geppetti P. Regulation of airway neurogenic inflammation by neutral endopeptidase.. Eur Respir J 1998 Dec;12(6):1454-62.
              pubmed: 9877509doi: 10.1183/09031936.98.12061454google scholar: lookup
            35. Cheung D, Bel EH, Den Hartigh J, Dijkman JH, Sterk PJ. The effect of an inhaled neutral endopeptidase inhibitor, thiorphan, on airway responses to neurokinin A in normal humans in vivo.. Am Rev Respir Dis 1992 Jun;145(6):1275-80.
              pubmed: 1317691doi: 10.1164/ajrccm/145.6.1275google scholar: lookup

            Citations

            This article has been cited 1 times.
            1. Morini M, Peli A, Rinnovati R, Magazzù G, Romagnoli N, Spadari A, Pietra M. Immunohistochemical Expression of Neurokinin-A and Interleukin-8 in the Bronchial Epithelium of Horses with Severe Equine Asthma Syndrome during Asymptomatic, Exacerbation, and Remission Phase. Animals (Basel) 2021 May 12;11(5).
              doi: 10.3390/ani11051376pubmed: 34066204google scholar: lookup
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