Involvement of endogenous tachykinins in LTD4-induced airway responses

J. Ishikawa, M. Ichinose, M. Miura, N. Kageyama, H. Yamauchi, M. Tomaki, Y. Sasaki, K. Shirato

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Leukotriene D4-(LTD4) has been reported to cause tachykinin release from airway sensory nerves. However, the functional significance of endogenously released tachykinins in LTD4-mediated airway responses has not been fully clarified. The aim of this study was to investigate whether LTD4-induced airway responses are due, in part, to tachykinin release in guinea-pigs. Airway plasma exudation and bronchoconstriction were assessed by measuring extravasation of Evans blue dye and by mean pulmonary resistance (RL) in the presence of atropine (1 mg · kg-a1 i.v.) and propranolol (1 mg · kg-1 i.v.), respectively. LTD4 (5 μg · mL-1 for 1 min) inhalation caused increase in plasma exudation and RL. Capsaicin pretreatment of animals to deplete sensory neuropeptides significantly inhibited LTD4-induced plasma exudation in the main bronchi, but not in the central (cIPA) and peripheral intrapulmonary airways (pIPA). Pretreatment with specific tachykinin neurokinin-1 (NK1)-receptor antagonists. FK 888 (10 mg · kg-a1 i.v.) and CP 96345 (4 mg · kg-a1 i.v.), also significantly reduced LTD4-induced plasma exudation in the main bronchi, and in the main bronchi and cIPA, respectively. However, these antagonists did not significantly affect the LTD4-induced increase in RL. In contrast, neurokinin-2 (NK2)-receptor antagonists, SR 48968 (0.3 mg · kg-1 .v.), significantly inhibited the bronchoconstriction after LTD4-inhalation. These results suggest that leukotriene D4-induced bronchoconstriction and plasma exudation in guinea-pigs are, in part, due to tachykinin release from airway sensory nerves.

Original languageEnglish
Pages (from-to)486-492
Number of pages7
JournalEuropean Respiratory Journal
Volume9
Issue number3
DOIs
Publication statusPublished - 1996 Mar

Keywords

  • asthma
  • leukotriene D-receptor
  • neurokinin-receptor
  • plasma leakage
  • sensory neuropeptides

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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