Stimulation of airway sensory nerves by cyclosporin A and FK506 in guinea-pig isolated bronchus

S. Harrison, S. Reddy, C. P. Page, D. Spina

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

1. We have investigated the contractile property of cyclosporin A and FK506 in guinea-pig isolated bronchus. 2. Cyclosporin A (10 μM) failed to significantly attenuate the excitatory non-adrenergic non-cholinergic (eNANC) and cholinergic contractile response (per cent methacholine E(max)) induced by electrical field stimulation (EFS). In contrast, eNANC responses were significantly attenuated by both the neurokinin (NK)-1 and (NK)-2 receptor antagonists, N-acetyl-L-tryptophan 3,5-bis (trifluoromethyl)-benzyl and SR48968, respectively. 3. Cyclosporin A and FK506 caused a concentration-dependent contraction in guinea-pig isolated bronchus, which was significantly attenuated by NK-1 and NK-2 receptor antagonists. The capsaicin receptor antagonist, capsazepine (10 μM) significantly reduced the contractile response to cyclosporin A and capsaicin, but not to FK506. 4. The N-type calcium channel blocker, ω-Conotoxin (ωCTX: 10 nM), significantly reduced the contractile response to FK506 and the eNANC response following EFS. In contrast, ω-CTX failed to significantly reduce the contractile potency to capsaicin or cyclosporin A. 5. In bronchial preparations desensitized by repeated application of capsaicin (1 μM), the contractile responses to both cyclosporin A (100 μM) and FK506 (100 μM), were significantly reduced. In contrast, the contractile responses to substance P and neurokinin A (10 μM) were not altered. Furthermore, repeated application of cyclosporin A (100 μM) significantly inhibited the contractile response to capsaicin (1 μM). 6. The findings from this study would indicate that cyclosporin A and FK506 mediate contraction of guinea-pig isolated bronchus secondary to the release of neuropeptides from airway sensory nerves. However, the release of sensory neuropeptides appears to be mediated via different mechanisms for cyclosporin A and FK506, the former by stimulation of the vanilloid receptor and the latter via opening of N-type calcium channels.

Original languageEnglish
Pages (from-to)1405-1412
Number of pages8
JournalBritish Journal of Pharmacology
Volume125
Issue number7
DOIs
Publication statusPublished - 01-01-1998

All Science Journal Classification (ASJC) codes

  • Pharmacology

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