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Small intestine
Involvement of tachykinin receptors in sensitisation to cow’s milk proteins in guinea pigs
  1. J Gaya,
  2. J Fioramontia,
  3. R Garcia-Villara,
  4. X Emonds-Altb,
  5. L Buenoa
  1. aDepartment of Pharmacology, Institut National de la Recherche Agronomique, 180 chemin de Tournefeuille, 31931 Toulouse, France, bSanofi Recherche, 371 rue du Pr J Blayac, 34184 Montpellier, France
  1. Dr Jean Fioramonti, INRA, Department of Pharmacology, BP 3, F-31931 Toulouse, France.

Abstract

BACKGROUND There is growing evidence for a pivotal role for tachykinins in gut neuroimmune interactions.

AIMS To determine whether NK1, NK2, and NK3 tachykinin receptors are involved in milk protein induced allergic sensitisation.

METHODS Eight groups of 12 Dunkin-Hartley guinea pigs (250–300 g) were used. Four groups were sensitised to milk proteins for three weeks. During this period, these animals were injected intraperitoneally each day with NK1 (SR 140333; 0.3 mg/kg), NK2 (SR 48968; 5 mg/kg), or NK3 (SR 142801; 5 mg/kg) receptor antagonist or vehicle. The fifth group had water available instead of milk and was used as a non-sensitised control. The three other groups received the NK receptor antagonists for three weeks but were not sensitised to milk proteins.

RESULTS Sensitised animals treated with NK1 and NK3 receptor antagonists had both lower IgE and IgG serum titres, evaluated by passive cutaneous anaphylaxis, and lower specific IgG serum titres, determined by enzyme linked immunosorbent assay (ELISA), than vehicle treated animals. Sensitisation induced an increase in intestinal mast cell number which was abolished by treatment with the NK1 receptor antagonist. Antigenic challenge-induced jejunal hypersecretion was also blocked by treatment with the NK1 receptor antagonist.

CONCLUSION In guinea pigs, NK1 and NK3 but not NK2 receptors are involved in sensitisation to cow’s milk. However, NK1 but not NK3 receptor antagonists abolish both the hypermastocytosis induced by food allergy and the hypersecretion induced by antigenic challenge, suggesting different roles for NK1 and NK3 receptors in the mechanisms of sensitisation to β-lactoglobulin.

  • NK receptors
  • tachykinins
  • food allergy
  • β-lactoglobulin sensitisation
  • sensitisation
  • guinea pig

  • Abbreviations

    SP
    substance P
    NK
    neurokinin
    PCA
    passive cutaneous anaphylaxis
    ELISA
    enzyme linked immunosorbent assay

    • https://doi.org/10.1136/gut.44.4.497

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    • Abbreviations

      SP
      substance P
      NK
      neurokinin
      PCA
      passive cutaneous anaphylaxis
      ELISA
      enzyme linked immunosorbent assay
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