Involvement of enhanced neurokinin NK3 receptor expression in the severe asthma guinea pig model.

Abstract

In this study, we investigated the involvement of neurokinin NK3 receptors in a severe asthma model prepared by administering ovalbumin via inhalation three times to systemically sensitized guinea pigs. [3H]senktide, a neurokinin NK3 receptor ligand, showed significant specific binding to the lungs from the model animals, but not to those from negative control animals. The airway responsiveness to intravenous neurokinin B, a neurokinin NK3 receptor agonist, was increased in the model, indicating an increase in functional NK3 receptors. Furthermore, SB 223956 ((-)-3-methoxy-2-phenyl-N-[(1S)-phenylpropyl]quinoline-4-carboxamide), a selective neurokinin NK3 receptor antagonist, significantly inhibited the ovalbumin-induced airway hyperresponsiveness to inhaled methacholine, but it did not show significant effects on the ovalbumin-induced airway narrowing and eosinophil accumulation. These results suggest that the expressed neurokinin NK3 receptors in the severe asthma model are involved in the development of airway hyperresponsiveness.

• Authors: Osamu Mukaiyama, Kiyoshi Morimoto, Emi Nosaka, Sakiko Takahashi, Makoto Yamashita
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 498 Issue 1-3 Pg. 287-94 (Sep 13 2004) ISSN: 0014-2999 [Print] Netherlands
• PMID: 15364007 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Benzamides
• Bronchoconstrictor Agents
• Peptide Fragments
• Piperidines
• Receptors, Neurokinin-3
• Methacholine Chloride
• Tritium
• senktide
• Substance P
• SR 48968
• Neurokinin B
• Ovalbumin

Topics

• Animals
• Asthma (immunology, metabolism)
• Benzamides (metabolism)
• Binding, Competitive
• Bronchoalveolar Lavage Fluid (cytology)
• Bronchoconstriction (drug effects)
• Bronchoconstrictor Agents (pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Eosinophils (drug effects, pathology)
• Guinea Pigs
• Lung (drug effects, pathology, physiopathology)
• Male
• Methacholine Chloride (pharmacology)
• Neurokinin B (pharmacology)
• Ovalbumin (immunology)
• Peptide Fragments (metabolism)
• Piperidines (metabolism)
• Receptors, Neurokinin-3 (antagonists & inhibitors, metabolism)
• Substance P (analogs & derivatives, metabolism)
• Tritium