Effect of BAY u3405, a thromboxane A2 receptor antagonist, on neuro-effector transmission in canine tracheal tissue

H. Aizawa, S. Takata, M. Shigyo, K. Matsumoto, H. Koto, H. Inoue, N. Hara

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Thromboxane A2 (TXA2) is reported to potentiate vagal nerve neuro-effector transmission in airway smooth muscle tissue. We investigated the effects of BAY u3405 (3(R)-[[4-fluorophenyl)sulfonyl]amino]-1,2,3,4,-tetrahydro-9H-carbazole- 9-propanoic acid), a potent and selective TXA2 receptor antagonist, on the increase in vagal nerve neuro-effector transmission induced by a TXA2 mimetic, U-46619, in the canine trachea. We measured the contractions of canine tracheal smooth muscle evoked by electrical field stimulation (EFS) and by acetylcholine (ACh) in the presence and absence of a subthreshold dose of U-46619 (the highest dose that did not induce any smooth muscle contraction). We then examined whether BAY u3405 inhibited the effect of U-46619 on tracheal smooth muscle. The following results were obtained: (i) subthreshold doses of U-46619 (10-10 M and 10-9 M) significantly increased the amplitude of the contractions evoked by EFS; (ii) by contrast, U-46619 had no effect on the contractile response of smooth muscle to exogenously applied ACh; (iii) the contraction evoked by EFS was completely abolished by the application of atropine (10-6 M) or tetrodotoxin (10-7 M), indicating that EFS caused the smooth muscle contraction through the release of ACh from vagal nerve terminals; and (iv) pretreatment with BAY u3405 (10-6 M) abolished the excitatory action of U-46619 on the amplitude of twitch contraction evoked by EFS in the trachea. These results indicate that U-46619, at low concentrations, has a prejunctional action stimulating neuro-effector transmission, presumably increasing ACh release from vagal nerve terminals through TXA2 receptors. The inhibitory action of BAY u3405 on the TXA2-induced enhancement of vagal nerve neuro-effector transmission may be useful in the treatment of bronchial asthma.

Original languageEnglish
Pages (from-to)213-217
Number of pages5
JournalProstaglandins, Leukotrienes and Essential Fatty Acids
Volume53
Issue number3
DOIs
Publication statusPublished - Sep 1995

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Cell Biology

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